*2.1.1 Genomic activity*

Estrogen binds to SHBG in the blood and in the interstitial fluid, where it penetrates the cell membrane and enters the cell nucleus and binds to receptors. These 2 genes are encoded for 2 estrogen isoforms α and β.

The hormone- receptors structures forms dimer (usually ERα-ERα, ERβ- ERβ or ERα- ERβ) that bind to a specific nucleotide sequence, namely, Estrogen-response elements (EREs) in regions that control different genes regulation of transcription [3] (see **Figure 1**).

Estrogen acts through several nuclear receptors. Estrogen affects the endometrium, the vagina and the breast [4]. And it interact with Calcitonin, parathyroid hormone, vitamin D and interleukin. Estrogen stimulates the division and growth of the skin cells, connective tissue and mucosal membrane [5].

#### *2.1.2 Non genomic activities*

The rapid effects of estrogen, such as the removal of Ca2+ granular cells and uterine blood-flow are mediated by non-genomic actions [3].

Non-genomic activity occur without bind to cellular receptors of estrogen. The beneficial effects of estrogen on blood vessels are an important non-genomic effect [5]. It affects not only blood vessels in the reproductive system, but also the cerebral, coronary and carotid arteries.

**5**

*Role of Sex Hormones in Human Body*

*DOI: http://dx.doi.org/10.5772/intechopen.95778*

vessels only in the presence of estrogen [6].

*Mode of progesterone action by genomic and non- genomic action.*

**2.2 Progesterone receptors**

**Figure 2.**

breast cancers [7].

shown in **Figure 2**.

androgen receptors.

**2.3 Androgen receptors**

Production of nitrous oxide, mediates vasodilation and endothelial protection.

Like estrogen, progesterone act through nuclear receptors, progesterone action

Like estrogen progesterone receptors has genomic and non -genomic activities as

Androgen is one of steroid hormone nuclear receptor family. The location of androgen receptors is on the X chromosome. And these receptors composed of 3 functional domains: the ligand binding domain, the DNA binding domain, and

The DBD is the most highly protected part among the various types of the steroid hormone receptors in the nucleus,while the N-terminal domain in androgen receptor is the mostly changeable. And due to the highly protected quality of DNA binding domain among steroid hormone receptors (nuclear receptors), and having selective androgen response elements, this will result in particular activation of the

N-terminal transcriptional regulation domain (**Figure 3**).

Estrogen also stimulates the production of prostacyclin vasodilating, prevents vasoconstriction and prevents platelet aggregation. Also Acetylcholine dilates blood

is by 2 isoform of progesterone receptors (PR-A and PR-B). These 2 isoforms differ in fact that PR-B has an extra (164) amino acid at N-terminal region termed the B-upstream segment,and this is absent in PR-A.And any mutations of amino acids in B-upstream segment lead to loss of PRB specific gene regulation activity. Normally in human tissues, PR-A and PR-B are as a rule present at same levels but impairment of this ratio regulation lead to tissue abnormalities like that occur in

#### **Figure 1.** *Genomic action of steroid hormones (estrogen) in the cell.*

#### **Figure 2.**

*Reproductive Hormones*

**2.1 Estrogen receptor**

*2.1.1 Genomic activity*

[3] (see **Figure 1**).

*2.1.2 Non genomic activities*

coronary and carotid arteries.

*Genomic action of steroid hormones (estrogen) in the cell.*

**2. Physiological effects of sex hormones**

genes are encoded for 2 estrogen isoforms α and β.

of the skin cells, connective tissue and mucosal membrane [5].

uterine blood-flow are mediated by non-genomic actions [3].

Sex hormones are chemical structures derived from cholesterol, and they are a group of steroidal hormones act as chemical messengers in the body. The activity of steroid hormones is carried out by receptors on extracellular proteins belonging to the family of nuclear substances. Through genomic and non-genomic action, these receptors intervene transduction of signals in a manner of specific context [2].

Estrogen binds to SHBG in the blood and in the interstitial fluid, where it penetrates the cell membrane and enters the cell nucleus and binds to receptors. These 2

The hormone- receptors structures forms dimer (usually ERα-ERα, ERβ- ERβ or ERα- ERβ) that bind to a specific nucleotide sequence, namely, Estrogen-response elements (EREs) in regions that control different genes regulation of transcription

Estrogen acts through several nuclear receptors. Estrogen affects the endometrium, the vagina and the breast [4]. And it interact with Calcitonin, parathyroid hormone, vitamin D and interleukin. Estrogen stimulates the division and growth

The rapid effects of estrogen, such as the removal of Ca2+ granular cells and

Non-genomic activity occur without bind to cellular receptors of estrogen. The beneficial effects of estrogen on blood vessels are an important non-genomic effect [5]. It affects not only blood vessels in the reproductive system, but also the cerebral,

**4**

**Figure 1.**

*Mode of progesterone action by genomic and non- genomic action.*

Production of nitrous oxide, mediates vasodilation and endothelial protection. Estrogen also stimulates the production of prostacyclin vasodilating, prevents vasoconstriction and prevents platelet aggregation. Also Acetylcholine dilates blood vessels only in the presence of estrogen [6].

#### **2.2 Progesterone receptors**

Like estrogen, progesterone act through nuclear receptors, progesterone action is by 2 isoform of progesterone receptors (PR-A and PR-B). These 2 isoforms differ in fact that PR-B has an extra (164) amino acid at N-terminal region termed the B-upstream segment,and this is absent in PR-A.And any mutations of amino acids in B-upstream segment lead to loss of PRB specific gene regulation activity. Normally in human tissues, PR-A and PR-B are as a rule present at same levels but impairment of this ratio regulation lead to tissue abnormalities like that occur in breast cancers [7].

Like estrogen progesterone receptors has genomic and non -genomic activities as shown in **Figure 2**.

#### **2.3 Androgen receptors**

Androgen is one of steroid hormone nuclear receptor family. The location of androgen receptors is on the X chromosome. And these receptors composed of 3 functional domains: the ligand binding domain, the DNA binding domain, and N-terminal transcriptional regulation domain (**Figure 3**).

The DBD is the most highly protected part among the various types of the steroid hormone receptors in the nucleus,while the N-terminal domain in androgen receptor is the mostly changeable. And due to the highly protected quality of DNA binding domain among steroid hormone receptors (nuclear receptors), and having selective androgen response elements, this will result in particular activation of the androgen receptors.

#### **Figure 3.**

*Functional domains of the androgen receptor (AR): N-terminal domain, DNA binding domain (DBD), ligand binding domain. AF-1 – Transcriptional activating function 1. AF-2 – Transcriptional activating function 2. H – Hinge region. NLS –nuclear localization signal. NES – Nuclear export signal.*

The dihydrotestosterone bind to the androgen receptors with a twofold and more affinity with less dissociation of about fivefold in comparison with testosterone.

Like estrogen and progesterone there are 2 ways of ligand-dependent androgen receptors action, DNA dependent (genomic) and DNA independent (nongenomic) binding (**Figure 4**).

The androgens have a crucial biological effects on, muscle, bone, adipose tissue,prostate, neural, cardiovascular, haemopoietic,immune, and the reproductive systems [8].

The biological effects of the AR mutation lead to insensitivity of receptors to androgens in men, resulting feminization of external genitalia of the male (XY female) [9].

Studies in animals with AR deficiency have shown that androgenic signaling is associated with a greater number of women with premature ovarian senility, associated with follicular atresia. Subsequent analysis of AR-free mice showed defects in lutenization of the ovarian follicle [10–12].

As a result of the development of the reproductive system, androgens (especially testosterone and 5α-dehydrotestosterone), induces and maintain secondary sexual characteristics, stimulate male reproductive activity and assist in the production of the sperms. The prostate epithelium is also sensitive for androgen, and androgen signaling is necessary to maintain cell homeostasis in the adult prostate. As the apoptosis in epithelial cells affects the prostate, can be altered by the supplementation of androgens [13].

A predictive model of AR in the prostate showed that strategic paracrine signals control the proliferation of epithelial cells [14].

**7**

**Table 1.**

*Role of Sex Hormones in Human Body*

growth factors signaling [16].

endometrium [17, 18].

tissues [1].

production.

**3.1 Cardiovascular system**

common in men than in women [19].

**Gonadal steroids Normal range, conventional units** Estradiol Women, basal 20–60 pg./mL

Progesterone Women, luteal phase 2–20 ng/mL

Dihydrotestosterone Women 0.05–0.3 ng/mL

Testosterone Women <1 ng/mL

*Normal ranges of sex steroid in male and female.*

*DOI: http://dx.doi.org/10.5772/intechopen.95778*

**3. The biological effects of sex steroids**

The effect of AR on the prostate pro-survival, plays a vital role in the pathogenesis of the prostatic cancers. It has been shown 75 years ago that prostate cancer

In many ways, this is due to the transport of androgens to the prostate, which are involved in metabolism, in the formation of the cell cycle and in the control of

In addition, the epithelial AR signal is correlated with an 'infection' in the prostate, which is independent of the parasitic AR signal in the stroma. AR increases VEGF-related angiogenesis and increases prostate growth, therefore, AR is an important treatment for prostate cancer. AR signaling has been shown to cause cancers in other organs, including breast, bladder, pancreas, ovary and

Although estradiol and progesterone levels vary during menstruation, estrogen

A significant lower risk of CVD has shown in premenopausal women than men and postmenopausal women. Estrogen support the vasodilation effect through relaxation of smooth muscle via increases the production of nitric oxide, which helps maintain low platelet activity, and the angiogenesis is stimulated by estrogen

Variation in the epidemiology, incidence and sequel of cardiovascular diseases in both sexes indicate changes in susceptibility to hereditary cardiovascular diseases that can result from several factors. In other cases, gender differences are important in expression of genes (especially X-chromosome genes), incidence of heart disease,as explained previously at the same age, cardiovascular disease is more

Women, ovulatory surge >200 pg./mL

Women, follicular phase <2 ng/mL

Men <50 pg./mL

Men <2 ng/mL

Men 0.25–0.75 ng/mL

Men 3–10 ng/mL

and progesterone levels are always higher in women than in men [1] (**Table 1**). Estradiol and progesterone have many effects depend on its relation to the venereal system. All steroid hormones have a great effect on the ovaries, fallopian tubes, uterus, external genitalia, hypothalamus and pituitary gland. Estrogen, progesterone and androgen, have significant effects on non-reproductive

regeneration occurs due to androgen deprivation after castration [15].

**Figure 4.** *Mechanisms of ligand-dependent androgen receptor (AR) action.*

#### *Role of Sex Hormones in Human Body DOI: http://dx.doi.org/10.5772/intechopen.95778*

*Reproductive Hormones*

testosterone.

**Figure 3.**

tive systems [8].

tion of androgens [13].

female) [9].

genomic) binding (**Figure 4**).

lutenization of the ovarian follicle [10–12].

control the proliferation of epithelial cells [14].

*Mechanisms of ligand-dependent androgen receptor (AR) action.*

The dihydrotestosterone bind to the androgen receptors with a twofold and more affinity with less dissociation of about fivefold in comparison with

*2. H – Hinge region. NLS –nuclear localization signal. NES – Nuclear export signal.*

Like estrogen and progesterone there are 2 ways of ligand-dependent androgen receptors action, DNA dependent (genomic) and DNA independent (non-

*Functional domains of the androgen receptor (AR): N-terminal domain, DNA binding domain (DBD), ligand binding domain. AF-1 – Transcriptional activating function 1. AF-2 – Transcriptional activating function* 

The androgens have a crucial biological effects on, muscle, bone, adipose tissue,prostate, neural, cardiovascular, haemopoietic,immune, and the reproduc-

The biological effects of the AR mutation lead to insensitivity of receptors to androgens in men, resulting feminization of external genitalia of the male (XY

Studies in animals with AR deficiency have shown that androgenic signaling is associated with a greater number of women with premature ovarian senility, associated with follicular atresia. Subsequent analysis of AR-free mice showed defects in

As a result of the development of the reproductive system, androgens (especially testosterone and 5α-dehydrotestosterone), induces and maintain secondary sexual characteristics, stimulate male reproductive activity and assist in the production of the sperms. The prostate epithelium is also sensitive for androgen, and androgen signaling is necessary to maintain cell homeostasis in the adult prostate. As the apoptosis in epithelial cells affects the prostate, can be altered by the supplementa-

A predictive model of AR in the prostate showed that strategic paracrine signals

**6**

**Figure 4.**

The effect of AR on the prostate pro-survival, plays a vital role in the pathogenesis of the prostatic cancers. It has been shown 75 years ago that prostate cancer regeneration occurs due to androgen deprivation after castration [15].

In many ways, this is due to the transport of androgens to the prostate, which are involved in metabolism, in the formation of the cell cycle and in the control of growth factors signaling [16].

In addition, the epithelial AR signal is correlated with an 'infection' in the prostate, which is independent of the parasitic AR signal in the stroma. AR increases VEGF-related angiogenesis and increases prostate growth, therefore, AR is an important treatment for prostate cancer. AR signaling has been shown to cause cancers in other organs, including breast, bladder, pancreas, ovary and endometrium [17, 18].
