The Development and Anatomy of Adrenal Glands

*Ravi Kant Narayan, Ashutosh Kumar and Manika Verma*

#### **Abstract**

The retroperitoneal adrenals are situated in the epigastric region of the abdomen, on the upper pole of either kidney. The glands are golden-yellow in color. The right adrenal is triangular or pyramidal, and the left one is semi-circular or crescentic in shape. The blood supply rate per gram of tissue for the adrenal gland is one of the highest. The two parts of the gland are derived from two different embryological tissues. This chapter discusses the normal macro- and microscopic anatomy of the gland along with its embryological development.

**Keywords:** adrenal, glands, retroperitoneal, microscopic anatomy, embryology

#### **1. Introduction**

The kidneys' fibrous capsule (renal fascia) wraps a wedged glandular and neuroendocrine tissue to its upper pole. These tissue masses are referred to as adrenal glands [1]. The adrenal glands were initially described in detail by Italian anatomist Bartolomeo Eustachi in 1563–1564. Adrenal is a Latin word where "*ad*" means "near", and "*ren*" means "kidney". The paired structure was termed "suprarenal", another Latin word where "*supra*" means "above", by Jean Riolan the Younger in 1629 [2]. These are endocrine glands, therefore, receive profuse blood supply via multiple arteries. In gross appearance, these are yellowish [3].

Adrenal glands have two major parts: the cortex and the medulla. These two parts share the similarity in their location, apart from which they differ in their ontogeny, phylogeny, architecture, and function [4]. In this chapter, the adrenals are discussed under the following headings:


#### **2. Location, external features, & coverings**

The retroperitoneal adrenals are situated in the epigastric region of the abdomen, on the upper pole of either kidney (**Figure 1**). The right adrenal being pyramidal in shape, has an apex, a base, two surfaces (anterior and posterior), and three borders (medial and

#### **Figure 1.**

*Illustration of the adrenal/ suprarenal gland's location on the upper pole of both kidneys and the blood supply of the glands (IVC – inferior vena cava, IPA – inferior phrenic artery, CT – coeliac trunk, SMA – superior mesenteric artery, SSA – superior suprarenal artery, MSA – middle suprarenal artery, ISA – inferior suprarenal artery).*

#### **Figure 2.**

*Sectional illustration of the renal fascia enveloping the kidney, and adrenal gland, extending to fuse with the diaphragmatic fascia.*

#### *The Development and Anatomy of Adrenal Glands DOI: http://dx.doi.org/10.5772/intechopen.108799*

lateral) [4]. The posteromedial surface is related to the diaphragm, and the inferior vena cava is on the anteromedial surface. Different aspects of the liver are related to the right adrenal; the right lobe of the liver lies anteriorly, while the bare area is located superior to the gland. The right kidney's upper pole is inferolateral to the endocrine structure. The crescentic left adrenal has two ends (narrow upper end and rounded lower end), two borders (medial and lateral), and two surfaces (anterior and posterior). The stomach lies anteriorly, the diaphragm posteromedially, and the kidney inferolateral [1].

The adrenals are surrounded by two sheaths, a layer of loose areolar tissue directly encapsulating the glands, and is composed of a significant quantity of fat. At the same time, the outer layer is the continuation of renal fascia, which also forms a thin septum separating the kidney from the adrenal above. An extension of the fascia connects the adrenal capsule's outer layer to the diaphragm's underlying peritoneal layer, which is attributed to the movement of the gland during respiration (**Figure 2**) [5].

#### **3. Gross appearance and microscopic architecture**

The size of the adrenal glands is around 5 cm long, 3 cm wide, and up to 1 cm thick. They weigh about 7 and 10 grams together in an adult person. The glands are golden-yellow in color (**Figure 3**) [3]. The right adrenal is triangular or pyramidal, and the left one is semi-circular or crescentic in shape. The external yellow-gold adrenal cortex and the inner brown-red adrenal medulla could easily be demarcated by gross examination of the cut surface of the adrenal gland [1, 6].

Microscopically, the adrenal cortex can be divided into three separate zones depending upon the arrangement of the cells (**Figure 4**). These are zona glomerulosa, zona fasciculata and zona reticularis. Each zone produces specific hormones pouring into the sinusoids running between the cells [7].

#### **3.1 Zona glomerulosa**

This is the outermost zone of the cortex, located just underneath the fibrous capsule. The cells are arranged in oval clusters giving the term "glomerulosa". Aldosterone

#### **Figure 3.**

*Image of adrenal glands, anterior (left) and posterior (right) surface, with scale for measuring length. Image courtesy: Mikael Häggström, MD. Public Domain (CC0 1.0).*

synthase, an enzyme, works primarily in this layer to produce the mineralocorticoid aldosterone, which is crucial for controlling blood pressure and maintaining salt concentration (**Table 1**) [5].

#### **3.2 Zona fasciculata**

The cells in this zone are organized in columns, or tape-like arrangements (hence the term 'fasciculata') radially orientated toward the medulla. It makes up around 80% of the cortex's volume, making it the thickest of the three layers. The fasciculata cells release glucocorticoids like cortisol, which regulates the metabolism of proteins, fats, and sugars (**Table 1**) [5].

#### **3.3 Zona reticularis**

The innermost layer of the adrenal cortex lies adjacent to the medulla. Here the tiny cells are arranged in the form of irregular cords and clusters (hence the term 'reticularis'). The capillaries and connective tissue can be found between these cords. These cells produce androgens in humans (**Table 1**) [5].

The central part of the gland, the medulla, contains chromaffin cells. These cells are the primary source of catecholamines, i.e., adrenaline and noradrenaline. The fightor-flight response is characterized by the effects of the catecholamines, which include elevated heart rate and blood pressure, constriction of blood vessels in the skin and

*The Development and Anatomy of Adrenal Glands DOI: http://dx.doi.org/10.5772/intechopen.108799*


**Table 1.**

*Secretions of adrenal gland zones, their effects, and their regulatory controls.*

gastrointestinal tract, dilatation of smooth muscle (bronchioles and capillaries), and increased metabolism (**Table 1**) [5].

#### **4. Arterial supply, venous & lymphatic drainage**

The blood supply rate per gram of tissue for the adrenal gland is one of the highest. This could only be achieved due to several arterial branches entering the gland, which are derived from three major branches (**Figure 1**) [8–10]:

a.Superior suprarenal artery - a branch of the inferior phrenic artery

b.Middle suprarenal artery - a direct branch of the abdominal aorta

c.Inferior suprarenal artery - a branch of the renal artery

On the contrary, each gland is drained by a single vein, namely

a.Right suprarenal vein which drains directly into the inferior vena cava

b.Left suprarenal vein which drains into the left renal or inferior phrenic vein.

The short cortical arteries form the subcapsular plexus branches. The plexus then provides an anastomosing network of capillary sinusoids that constitute the cortex's vascular system. These sinusoids infiltrate between the cords of zona fasciculata and then create the deep plexus in the zona reticularis, where they drain into minute venules that confluence with the principal vein of the medulla [7].

The medulla receives blood from two sources, the arterial medullary arterioles and the venous cortical sinusoidal capillaries, which have already fed the cortex and are high in adrenocorticosteroids. Long cortical arteries drop through the cortex from the subcapsular plexus and ramify into a dense network of dilated capillaries around the medullary secretory cells. The medullary capillaries then drain into the central medullary vein. Subsequently, the venous drainage of the cortex also supplies the medullary cells while crossing through the medulla on their way to the central medullary vein. The corticosteroids in the cortical venules are thought to significantly impact the medulla's ability to synthesize adrenaline [5, 7].

The lymph from the paired glands drains into lateral aortic nodes. The lymphatic vessels have been observed in the capsule, the connective tissue around the larger blood vessels, and the parenchyma of the adrenal medulla [11].

#### **5. Nerve innervations**

The adrenal is a neuroendocrine gland, i.e., the gland is regulated by both the pituitary hormones and nerve innervations. The cortical part of the gland is under the regulation of adrenocorticotrophic hormone released by the anterior lobe of the pituitary [5].

The adrenal medulla is considered a modified sympathetic ganglion as it is innervated by the myelinated pre-ganglionic sympathetic fibers coming from T5–T11 (splanchnic nerves) spinal levels and pours its secretion into the sinusoids, unlike other sympathetic ganglions [5].

#### **6. Development**

Either part of the adrenal gland is derived from two different embryological tissues. The adrenal cortex is derived from proliferated mesothelial cells around 5–6 weeks post-conception, while the medulla originates from the neural crest (**Figure 5**). The foetal adrenal cortex surrounds the growing adrenal medulla, and the entire gland is enclosed in a mesodermal layer that isolates it from the nearby developing gonad and kidney. The foetal adrenal cortex separates into two histologically distinct zones at about 9 weeks gestation: the definitive and foetal zones. Between the definitive and foetal zones, a third layer, the transitional zone, develops in the third trimester. The zona glomerulosa, the adrenal cortex's outer layer that generates mineralocorticoids, and the zona fasciculata, which produces glucocorticoids, are formed by 6 months of age from the definitive and transitional zones. The foetal cortex involutes throughout the first year of life, and the zona reticularis, which generates androgens, develops as the adrenal cortex's innermost layer. By 3 to 4 years, the zona reticularis differentiates into a separate layer (**Figure 6**) [6, 12].

It is interesting to note that medullary and cortical tissues combine to form a single organ in mammals, whereas they form into two separate organs in pre-vertebrates. The migration of medullary cells into the cortex, which starts in the seventh week of

*The Development and Anatomy of Adrenal Glands DOI: http://dx.doi.org/10.5772/intechopen.108799*

#### **Figure 5.**

*Illustration of magnified view of a foetal section showing the developmental tissues of the adrenal cortex and medulla.*

**Figure 6.**

*Illustration of the timeline for the development of the zones of the adrenal cortex and the medulla in a foetus.*

pregnancy, allows the primitive medullary and cortical cells to unite to form the adrenal gland. By the second trimester, the foetal adrenal cortex surrounds the medulla, and the entire gland is encased by a mesodermal layer, which isolates the adrenal glands from the nearby retroperitoneal structures [6, 13, 14].

#### **Author details**

Ravi Kant Narayan1 \*, Ashutosh Kumar2 and Manika Verma<sup>3</sup>

1 Dr.B.C. Roy Multi Speciality Medical Research Centre, IIT Kharagpur, India


\*Address all correspondence to: narayanintouch@gmail.com

© 2022 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

*The Development and Anatomy of Adrenal Glands DOI: http://dx.doi.org/10.5772/intechopen.108799*

#### **References**

[1] Standring S. Kidney and ureter. In: Gray's Anatomy [Internet]. 41st ed. London: Elsevier; 2016. [cited 2022 Sep 23] p. 1239-1240. Available from: https:// www.elsevier.com/books/grays-anatomy/ standring/978-0-7020-7705-0

[2] Schmidt JE. Medical discoveries: Who and when: A dictionary listing thousands of medical and related scientific discoveries in alphabetical order, giving in each case the name of the discoverer, his profession, nationality, and floruit, and the date of the discovery. Springfield (Ill.): Charles C. Thomas; 1959. p. 555

[3] Neville AM, O'Hare MJ. The Human Adrenal Cortex [Internet]. 1st ed. London: Springer London; 1982 [cited 2022 Sep 23]. Available from: http://link. springer.com/10.1007/978-1-4471-1317-1

[4] Kidneys SV. Ureters, and Suprarenal Glands. In: Textbook of Anatomy: Abdomen and Lower Limb. 2nd ed. New Delhi: Elsevier India; 2014. pp. 180-181

[5] Moore KL, Dalley AF, Agur AMR. Clinically Oriented Anatomy. Philadelphia: Lippincott Williams & Wilkins; 2013. p. 1171

[6] Vasudevan S, Brandt ML. Adrenal gland embryology, anatomy, and physiology. In: Ledbetter DJ, Johnson PRV, editors. Endocrine Surgery in Children [Internet]. Berlin, Heidelberg: Springer; 2018 [cited 2022 Sep 23]. pp. 77-85. DOI: 10.1007/978-3-662-54256-9\_7

[7] Young B, Woodford P, O'Dowd G. Adrenal glands. In: Wheater's Functional Histology: A Text and Colour Atlas. 6th ed. London, England: Churchill Livingstone; 2013. pp. 328-321

[8] Narayan RK, Asghar A, Ghosh SK, Bharti S. Adrenal myelolipoma mimics ectopic adrenal or renal tissue: An incidental finding during cadaveric dissection. Acta Endocrinol Buchar Rom. 2021;**17**(1):111-116

[9] Priya A, Narayan R, Ghosh S. Prevalence and clinical relevance of the anatomical variations of suprarenal arteries: A review. Anatomy & Cell Biology. 2022;**55**(1):28-39. DOI: 10.5115/ acb.21.211

[10] Priya A, Narayan R, Ghosh S. Unilateral variations of inferior phrenic and suprarenal arteries: A case study with commentary on its clinical importance. Translational Research in Anatomy. 1 Nov 2021;**25**:100147. DOI: 10.1016/j.tria.2021.100147

[11] Ross M, Pawlina W. Endocrine organs. In: Histology: A Text and Atlas. 7th ed. London: Wolters Kluwer Health; 2016. pp. 767-768

[12] Mitty HA. Embryology, anatomy, and anomalies of the adrenal gland. Seminars in Roentgenology. 1988;**23**(4):271-279

[13] Avisse C, Marcus C, Patey M, Ladam-Marcus V, Delattre JF, Flament JB. Surgical anatomy and embryology of the adrenal glands. The Surgical Clinics of North America. 2000;**80**(1):403-415

[14] Barwick TD, Malhotra A, Webb JAW, Savage MO, Reznek RH. Embryology of the adrenal glands and its relevance to diagnostic imaging. Clinical Radiology. 2005;**60**(9):953-959

## **Chapter 2** Adrenal Cortex Hormones

*Ali Gamal Ahmed Al-kaf*

#### **Abstract**

Over 50 different steroids, including precursors to other steroid hormones, are secreted by the adrenal glands, which are located directly above the kidneys. Aldosterone and hydrocortisone, however, are the two most significant hormonal steroids created by the adrenal cortex. Since aldosterone is too expensive to produce commercially, other semi-synthetic analogues are now used to treat Addison's disease in its place. Fludrocortisone, for example, greatly increases both salt retention and antiinflammatory activity when combined with hydrocortisone. The kidneys' ability to reabsorb sodium is increased by aldosterone. Increased blood volume will follow an increase in plasma sodium concentration. Additionally, aldosterone boosts potassium ion excretion. Addison's disease is brought on by inconsistency. Glycogen storage synthesis is induced by the synthesis of glycogen synthase, and gluconeogenesis (the production of glucose from glucose) is induced in the liver.

**Keywords:** steroid hormones, adrenal glands, synthesis, metabolism, structure-activity relationship, mechanism and activity

#### **1. Introduction**

Over 50 different steroids, including precursors to other steroid hormones, are secreted by the adrenal glands, which are located directly above the kidneys. Aldosterone and hydrocortisone, however, which are the most significant hormonal steroids produced by the adrenal cortex, are only used to treat Addison's disease [1]. An 11-OH and an 18-CHO in the naturally occurring hormone aldosterone naturally bridge to form a hemiacetal.

Because aldosterone is too expensive to produce commercially, other semisynthetic analogues are now used to treat Addison's disease instead [1].

Fludrocortisone, for example, greatly increases both salt retention and antiinflammatory activity when added to hydrocortisone [2, 3].

They also secrete a number of vital hormones that are crucial for maintaining a healthy immune system, metabolic rate, and salt and water balance in the body (**Tables 1**–**5**).


#### **Table 1.**

*Chemical structure of steroid hormones [3].*


#### **Table 2.**

*Results of the reaction between corticosteroids with conc. H2SO4 [3–5].*


#### **Table 3.**

*Conditions of spectrophotometric determination of corticosteroids [3–5].*


#### **Table 4.**

*Effects of substituents on glucocorticoid activity.*


#### **Table 5.**

*Enhancement factors for various functional groups of corticosteroids.*

#### **2. Chemistry of steroid hormones**

The general formula for the basic structure of the steroid compounds may be represented as follows [3].

#### **2.1 General steroid formula**

In 1956, N.N. Suvoroviy with his colleagues (Allunion Scientific Research of Chemical and Physical Institute) were shown the ability of obtaining cortisone from solasodine from the plant *Solanum* [3, 4].

Corticosteroids may be differentiated from each other by reaction on this or other functional groups [3].

By heating on water bath, spiritus solutions of corticosteroids with phenylhydrazine solution formed yellow color. This reaction occurred with ketonic group, for example [3].

*Adrenal Cortex Hormones DOI: http://dx.doi.org/10.5772/intechopen.106785*

Reaction for obtaining acetohydroxamic acid which reacts with iron salts (III) formed compounds colored in dark cherry (cortisone acetate) or red-brown color (dezoxycortone acetate) [3].

Acetyl group may be detected after hydrolysis of cortisone and hydrocortisone acetate in spiritus solution of hydroxid potassium and subsequent addition of conc. Sulfuric acid which forms ethyl acetate with characteristic odor. For identification of hydrocortisone acetate: [3].

The adrenal glands (which lie just above the kidneys) secrete over 50 different steroids, including precursors to other steroid hormones. However the most important hormonal steroids produced by the adrenal cortex are aldosterone and hydrocortisone [6–11].

#### **2.2 Mineralocorticoids**

They are used only for treatment of Addison's disease. The naturally occurring hormone aldosterone has an 11 β-OH and an 18-CHO that naturally bridge to form a hemiacetal [7–13].

Aldosterone is too expensive to produce commercially; therefore other semisynthetic analogues have taken its place for treatment of Addison's disease [12].

Adding a 9 α-halogen to hydrocortisone (e.g. Fludrocortisone) greatly increases both salt retention and anti-inflammatory activity [2, 3].

The following table summarizes the relative effect of various substituents on salt retention and glucocorticoid activity. The salt-retaining actions are approximately additive. For example, a 9 α-fluoro group's + + + increase in salt retention can be eliminated by 6 α-methyl's - - - [2, 14–16].

#### **2.3 Glucocorticoids with moderate to low salt retention**

The glucocorticoids with moderate to low retention include cortisone, hydrocortisone, and their 1-enes prednisolone and prednisone [2, 14–16].

An 11-OH maintains good topical anti-inflammatory activity, but 11-ones have little or none [2, 3, 14–16].

The 1-ene of prednisolone and prednisone increases anti-inflammatory activity by about a factor of 4 and somewhat decreases salt retention [2, 3, 14–16] (**Figures 1**–**13)**.

The 11 β-OH of hydrocortisone is believed to be of major importance in binding to the receptors. Cortisone may be reduced in vivo to yield hydrocortisone as the active agent [2, 3, 14–16, 19–22].

Introduction of fluoro (F) to C6α and C9α positions increase both mineralocorticoid and glucocorticoid activity due to the electron-withdrawing inductive effect on the 11β-OH making it more acidic, therefore, better able to form noncovalent bonds with the receptor. A 9α-halo substituent also reduces oxidation of the 11 β-OH to the less active 11-one [2, 3, 14–16, 19–22].

**Figure 1.** *Structure of adrenal gland.*

#### **Figure 2.**

*(Left) Cells of the zona glomerulosa produce hormones called mineralocorticoids because they affect salt balance. Aldosterone is the most important. Among its functions are sodium retention and potassium excretion by the kidneys. (Right) The cortex secretes three families of steroid hormones: mineralocorticoids, glucocorticoids, and androgens. Note that each is produced by a different group of cells. The medulla secretes amine hormones known as catecholamines.*

#### *Adrenal Glands – The Current Stage and New Perspectives of Diseases and Treatment*

#### **Figure 3.**

*(Left) Cells of both zona fasciculata and zona reticularis produce a family of hormones called glucocorticoids because they regulate glucose metabolism. This family includes cortisol, cortisone, and corticosterone. Only cortisol is secreted in significant amounts in humans. In addition to regulating energy metabolism, cortisol regulates the immune system and facilitates the stress response. (Right) Cells of both zona fasciculate and zona reticularis also produce a family of hormones called androgens. Androgens are male sex hormones that include androstenedione and testosterone. Active secretion at puberty in both sexes causes the early growth spurt and appearance of axillary and pubic hair. Androgens are also responsible for sex drive in females.*

**Figure 4.** *Functional anatomy and zonation.*

#### **2.4 Glucocorticoids with very little or no salt retention**

They include 16 α-hydroxy (Triamcinolone); 16 α-, 17 α-ketal; (Amcinolone, Desonide, Flunisolide, Triamcinolone acetonide, Flucinolone acetonide, Flurandrenolide) [2, 14–16, 23].

#### *Adrenal Cortex Hormones DOI: http://dx.doi.org/10.5772/intechopen.106785*


#### **Figure 5.**

*Synthesis of the adrenal cortical hormones.*

Triamcinolone is converted to acetonide derivative (ketal) by reaction of acetone in the presence of strong acid. The latter is used only locally (topically) [2, 14–16].

They include also 6 α-methyl (methyl prednisolone); 16 α-methyl (Dexamethasone, Alclomethasone, Flumethasone) and 16 β-methyl (Betamethasone, Diflorasone, Paramethasone, Beclomethasone) [2, 3, 14–16, 23].

Other substituents have been found to significantly increase both glucocorticoid and mineralocorticoid activities: 1-ene; 2 α-methyl; 9 α-fluoro; 9 α-chloro; and 21-hydroxy [2, 3, 14–16].

In every case a 16-hydroxy or methyl (to eliminate salt retention) has been combined with another substituent to increase glucocorticoid or anti-inflammatory activity [2, 3, 14–16].

A primary goal of these highly anti-inflammatory drugs has been to increase topical potency [6, 7, 12].

#### **2.5 Risk of systemic absorption**

Except for fludrocortisones, the topical corticosteroids do not cause absorption effects when used on small areas of intact skin [6, 7, 12].

The adrenocortical steroids are contraindicated or should be used with great caution in patients having: [2, 3, 6–8, 10–12, 24, 25].

1.Peptic ulcer (in which the steroids may cause hemorrhage)

**Figure 6.** *The synthesis of steroids in the adrenal cortex.*


*Adrenal Cortex Hormones DOI: http://dx.doi.org/10.5772/intechopen.106785*

**Figure 7.**

*Cortisol feeds back to both the anterior pituitary to inhibit secretion of ACTH, and to the ventral hypothalamus to inhibit secretion of CRH.*

#### 6.Glaucoma

#### 7.Osteoporosis

#### 8.Herpes simplex involving the cornea

When glucocorticoids are topically administrated, their anti-inflammatory action can mask symptoms of infection.

If absolutely necessary to use the glucocorticoids topically during pregnancy, they should be limited to small areas of intact skin and used for a limited time.

#### **3. The adrenal glands**

#### **3.1 Introduction**

Pyramid-shaped organs in pairs.

Placed on each kidney's upper poles.

3–5 cm in length on average, weighing 1.5–2.5 gm.

The outer cortex, which is composed primarily of mesodermal tissue and makes about 90% of the weight of the adrenals [26].

The inner medulla (derived from a subpopulation of neural crest).

The adrenal gland is made up of the cortex and medulla. The cortex produces steroid hormones including glucocorticoids, mineralocorticoids, and adrenal

**Figure 8.**

androgens, and the medulla produces the catecholamines, epinephrine, and norepinephrine [26].

The body's adaptive response to stress is regulated by the adrenal glands' role in maintaining homeostasis in maintaining the balance of Na and K in the body's water blood pressure regulation [26].

#### **3.2 The main hormones**

1.The hormones called steroid (glucocorticoids, mineralocorticoids, androgens).

2. Secondly, catecholamines (norepinephrine, epinephrine).

The two different embryologic origins of the AG have an impact on the mechanisms that each of the two components uses to regulate the production of hormones [17, 26].

#### **Figure 9.**

*The impact of angiotensin II on the production of aldosterone.*

#### **3.3 Functional anatomy and zonation**

Three histologically distinct zones can be found in the adrenal cortex, arranged from outside to inside [27]:


The adrenal cortex secretes the following hormones:


#### **Figure 10.**

*The adrenal medulla is a modified sympathetic ganglion that produces a family of amine hormones called catecholamines. The two main hormones are epinephrine (E) and norepinephrine (NE). Epinephrine is 4-5 times more abundant than NE. The adrenal medulla [17, 18].*


#### **Figure 11.**

*Catecholamine physiologic effects [17, 18].*


#### **Figure 12.**

*Catecholamine-mediated responses to hypoglycemia [17, 18].*


#### **Figure 13.**

*Effects of epinephrine vs. norepinephrine [17, 18]. "" negative inhibitory effect; "+" positive stimulatory effect; and "0" no effect.*

#### **3.4 Zonation**

The adrenal cortex's zonafasciculata and zonareticularis are where the glucocorticoids cortisol and corticosterone, as well as the androgen dehydroepiandrosterone, are synthesized [27].

The zonaglomerulosa of the adrenal cortex is where mineralocorticoid aldosterone is made [27].

#### **3.5 Synthesis of the adrenal cortical hormones**

Four CYP enzymes (cytochrome P450 enzymes = a large family of oxidative enzymes with a maximum 450 nm absorbance when complexed with carbon monoxide) convert cholesterol into adrenal steroid hormones [28]. Cholesterol esters stored in the cells are used to synthesize the adrenal cortical hormones [28].

LDL particles in the blood are the main source of stored cholesterol, but the AG can also produce it entirely from scratch using acetate [28].

The first step in the synthesis of all adrenal steroids, which happens in each of the three zones of the cortex, is the conversion of cholesterol to pregnenolone in mitochondria. Enzymes that produce steroids [28].

#### **3.6 Genetic defects in adrenal steroidogenesis**

Can result in either relative or absolute deficiencies in the enzymes necessary for the biosynthesis of steroid hormones [29].

Changes in the types and quantities of steroid hormones secreted by the adrenal cortex are the direct results of these defects. In the end, disease results [29].

The majority of steroidogenic enzyme-related genetic flaws hinder cortisol production [29].

A decrease in blood cortisol levels prompts the release of ACTH, which has a growth-promoting effect on the adrenal cortex, causing either congenital adrenal hyperplasia or adrenal hypertrophy [29].

#### **3.7 Transport of adrenal steroids in blood**

A steroid hormone is prevented from being absorbed by cells or from being excreted in the urine by binding to a circulating protein molecule [18].

The blood is cleared of circulating steroid hormone molecules that are not bound to plasma proteins because they are free to interact with cell receptors [18].

Bound hormone separates from its binding protein and adds more free hormone to the system [18].

The half-lives of adrenal steroid hormones in the body are very long (from many minutes to hours) [18].

#### **3.8 Metabolism of adrenal steroids**

After being structurally altered to reduce their hormone activity and increase their water solubility, adrenal steroid hormones are primarily excreted from the body through the urine (primarily in the liver) [29]. Adrenal steroids are primarily metabolized in the liver where they are conjugated to glucuronic acid and eliminated in the urine [29].

#### **3.9 Control over the production of adrenal steroids**

By increasing intracellular cAMP, ACTH increases glucocorticoid and androgen synthesis in the zonafasciculata and zonareticularis of the adrenal cortex (cAMPactivates protein kinase A, which phosphorylates proteins that regulate steroidogenesis) [18].

On these cells, ACTH also has a trophic effect [18].

Angiotensin II increases cytosolic calcium and activates protein kinase C in the cells of the zonaglomerulosa to stimulate aldosterone synthesis [18].

ACTH's primary effects on steroidogenesis [18].

When ACTH binds to plasma membrane receptors, stimulatory G proteins connect those receptors to adenylyl cyclase (AC) (Gs).

Protein kinase A (PKA) is activated by cAMP in the cells, which phosphorylates specific proteins (PProteins). The expression of the genes for steroidogenic enzymes is stimulated and steroidogenesis is presumably started by these proteins.

*Adrenal Cortex Hormones DOI: http://dx.doi.org/10.5772/intechopen.106785*

The expression of the genes for steroidogenic enzymes is stimulated and steroidogenesis is presumably started by these proteins [18].

The impact of angiotensin II on the production of aldosterone [18].

Angiotensin II (AII) binds to receptors on the plasma membrane of zonaglomerulosa cells. Phospholipase C (PLC), which is connected to the angiotensin II receptor by G proteins, is activated as a result (Gq) [18].

In the plasma, PLC hydrolyzes phosphatidylinositol 4,5 bisphosphate (PIP2) membrane, resulting in the production of IP3 and diacylglycerol (DAG) [18].

#### **3.10 Intracellularly bound Ca2 is moved by IP3**

Protein kinase C (PKC) and calmodulin-dependent protein kinase are both activated by an increase in Ca2 and DAG (CMK) [18]. These enzymes phosphorylate the proteins (P-Proteins) that start the synthesis of aldosterone [18].

#### **4. Process of action**

Target cells' cytosol contains glucocorticoid receptors, which glucocorticoids bind to [18]. The glucocorticoid-bound receptor moves to the nucleus where it attaches to DNA glucocorticoid response elements to alter the transcription of particular genes [18]. The body must have access to glucocorticoids in order to adjust to stress, injury, and fasting [18].

Glucocorticoids

Very powerful and responsible for about 95% of all glucocorticoid activity is cortisol [18].

About 4% of the total glucocorticoid activity is provided by corticosterone, which is significantly less potent than cortisol [18].

Cortisone, which is nearly as potent as cortisol [18].

Synthetic, four times as potent as cortisol, prednisone [18].

Synthetic methylprednisone, which has five times the potency of cortisol [18]

(Synthetic, 30 times more potent than cortisol) Dexamethasone [18].

Glucocorticoids' effects [18].

Catabolic, anti-anabolic, and diabetogenic effects on metabolism.

Glucocorticoids' Anti-Inflammatory Properties.

The Immune System's Impact.

Protection of the Norepinephrine-Induced Vascular Response.

Stress Glucocorticoids.

Glucocorticoid Secretion Control.

Glucocorticoids Are Involved in the Responses to Injury, Stress, and Fasting [18]. Effects of cortisol on the metabolism of carbohydrates: [18]

Stimulation of Gluconeogenesis - Cortisol increases the enzymes needed in the liver cells to convert amino acids into glucose [18].

Cortisol causes the extrahepatic tissues, primarily muscle, to release amino acids [18].

Cells' Utilization of Glucose is Reduced [18].

"Adrenal Diabetes" and Increased Blood Glucose Concentration [18].

Cortisol's Impact on Protein Metabolism [18].

Protein Cellular Reductionin.

Plasma and Liver Protein Levels are Raised by Cortisol a rise in blood amino acids, a decline in amino acid transport into extrahepatic cells, and an improvement in transport into hepatic cells.

Cortisol's Impact on Fat Metabolism [18].

Mobilization of Fatty Acids Excess Cortisol Leads to Obesity.

Cortisol Helps the Body Fight Stress and Inflammation.

Effects of High Cortisol Levels on Inflammation.

Cortisol Prevents the Development of Inflammation through Other Effects and Lysosome Stabilization.

Cortisol Leads to Inflammation Healing.

The Inflammatory Response to Allergic Reactions is Blocked by Cortisol.

Effects of cortisol in reducing inflammation.

The lysosomal membranes are stabilized by cortisol.

Capillary permeability is lessened by cortisol.

White blood cell migration into the inflamed area and phagocytosis of the aged cells are both decreased by cortisol.

Cortisol significantly reduces lymphocyte production by suppressing the immune system.

Cortisol reduces interleukin-1 release from white blood cells, which is the primary mechanism by which it lowers fever.

Mineralocorticoids [18].

Aldosterone (very potent, accounts for about 90 percent of all mineralocorticoid activity).

Deoxycorticosterone (1/30 as powerful as aldosterone, but secreted in very small amounts).

Corticosterone (slight mineralocorticoid activity).

9α-Fluorocortisol (synthetic, slightly more potent than aldosterone).

Cortisol (very slight mineralocorticoid activity, but large quantity secreted).

Cortisone (slight mineralocorticoid activity).

Mineralocorticoids' effects [18].

Aldosterone stimulates sodium reabsorption in the kidneys by the distal tubule and collecting duct of the nephron and promotes the excretion of potassium and hydrogen ions, according to its physiological action.

Since potassium directly affects zona glomerulosa cells, an increase in the concentration of potassium in extracellular fluid stimulates aldosterone secretion.

Aldosterone Secretion Control.

The extracellular fluid's increased potassium ion concentration significantly boosts aldosterone secretion.

Aldosterone secretion is also significantly increased by an increase in the extracellular fluid's angiotensin II concentration.

Aldosterone secretion is very slightly reduced when the extracellular fluid's sodium ion concentration rises.

Aldosterone secretion requires ACTH from the anterior pituitary gland, but it has little impact on regulating the rate of secretion in most.

The catecholamines epinephrine (adrenaline) and norepinephrine (noradrenaline).

Four adrenergic receptors (alpha 1, 2, beta 1, 2) interact with catecholamines to mediate the effects of the hormones on cells.

Catecholamines have immediate and extensive effects.

Catecholamines are released from the chromaffin cells as a result of impulses generated in the cholinergic preganglionic fibers that innervate them by stimuli like injury, rage, pain, cold, strenuous exercise, and hypoglycemia.

Catecholamines promote the production of glucose in the liver, the release of lactate from muscle, and the breakdown of fat in adipose tissue to combat hypoglycemia.

#### **5. Conclusion**

The body's defense mechanisms depend heavily on the adrenal glands.

They trigger physiological adjustments that are required to combat changes in the environment outside the body. They also secrete a number of vital hormones that are crucial for maintaining a healthy immune system, metabolic rate, and salt and water balance in the body. Additionally protecting the body from stress. High levels of glucocorticosteroid production in response to stress can result in a 95 percent reduction in thymus gland size. It has not yet been completely determined how glucocorticoid stimulation protects against stress.

### **Author details**

Ali Gamal Ahmed Al-kaf Faculty of Pharmacy, Medicinal Chemistry Department, Sana'a University, Yemen

\*Address all correspondence to: alialkaf21@gmail.com

© 2022 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Section 2
