**4. Human foetal adrenal gland**

**Figure 2.** Steroid hormone and catecholamine location in the adrenal gland. The activating and negative feedback implicated mechanisms are shown. CRH, corticotropin-releasing hormone, ACTH, adrenocorticotropic hormone. Red

Similar effects as aldosterone

lines, inhibition; Green lines, activation. Modified from Nelson and Cox [26].

72 Umbilical Cord Blood Banking for Clinical Application and Regenerative Medicine

Increases amino acids use

Delays water elimination

Increases urea Heart and circulation Increases heart contraction strength

Metabolism Increases glycaemia

Kidneys Maintains glomerular flux

**Table 1.** Effects of cortisol on different systems.

**System Action High concentrations**

Increases peripheral vasoconstriction Induce angiotensinogen formation Stomach Increases gastric juices Gastric ulcer

Brain Hypothalamus inhibition

Immune system Anti-allergic and anti-inflammatory

Glucocorticoids interact on receptors located on skeletal, smooth, and cardiac muscles, brain, stomach, kidney, liver, lung, adipose and lymphatic cells. Those hormones bind to both mineralocorticoid and glucocorticoid receptors (MR and GR, respectively), members of the nuclear receptor's superfamily. GR are expressed since the embryonic stage [28]. GR are expressed in pancreas, liver, visceral adipose tissue, skeletal muscle and in brain areas such as

The human foetal adrenal gland has double weight than the foetal kidneys and after delivery its size decreases from 8 to 5 g in 5 weeks. It has three areas: foetal area, definitive area and medulla. The foetal area is integrated by vast cells presenting steroid synthesis characteristics. This area occupies approximately the 80% of the total adrenal gland at the end of pregnancy. It secretes two main substances: dehydroepiandrosterone sulphate (DHAS), synthesized in the foetal area, and cortisol, synthesized in the definitive area [16, 21]. DHAS is synthesized from acetate or from cholesterol (**Figure 1**). It can be also formed by direct conversion from other steroid sulphates, beginning from cholesterol sulphate. The DHAS production increases as the pregnancy goes by. Its production is kept high during the first week after delivery, and then decreases, reflecting the foetal area's atrophy. After delivery, at the age of 1 year, total involution of the foetal area is observed [3, 35].

The step from DHAS to 16-α-hydroxydehydroepiandrosterone (16-α-OH-DHAS) is scarce in the foetal adrenal gland, but it can be observed in the foetal liver. Afterwards, both substances are used as substrates in the placenta for the oestrogens' synthesis: DHAS produces oestradiol and 16-α-OH-DHAS produces oestriol (see **Figure 1** footnote). In the definitive area, cortisol can be synthesized from maternal progesterone or de *novo* from LDL cholesterol. It is not known what of the two pathways is the most used. It seems that the foetal adrenal gland has small capability for progesterone secreting and there is a 3-OH steroid dehydrogenase– isomerase complex deficiency. The cortisol synthesis grows along pregnancy: 6.9 ng/mL in 13 week foetuses' cord blood and 70 ng/mL at the end of gestation [16, 21].

The definitive area secretes deoxycorticosterone and aldosterone. These secretions begin at 10– 20 weeks and increase until the end of pregnancy. There is great cortisol transference from mother to foetus through the placenta. Most of this cortisol can be found in the foetus as corticosterone. Corticosterone levels in foetus are 5–10 times higher than in the mother's blood. Cortisol is also transferred from foetus to mother. Cortisol can be formed from cortisone in foetus, as some tissues as kidney, lung, amniotic membrane and liver have the 11-hydroxysteroid dehydrogenase (11-HSD) [16].
