**6. Carbohydrate metabolism: pancreatic hormones**

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

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-

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-hydroxys-

**5. Regulation of the secretions of the definitive and foetal areas in the**

Both the foetal and the definitive areas of the adrenal gland are stimulated by ACTH and αmelanocyte stimulating hormone (MSH). Both hormones are secreted by the foetal pituitary gland [16, 35]. As possible stimulators of the adrenal gland, angiotensin, prolactin, growth hormone (GH) and epidermal growth factor have also been suggested. Progesterone and deoxycorticosterone secretions decrease as pregnancy goes by, suggesting that the enzymatic systems for their transformation into aldosterone and cortisol become active, as these hor-

With respect to the medulla secretions, it is known that the corticosterone synthesized *in situ* by the foetus is required for negative feedback suppression of the hypothalamus-pituitaryadrenal axis and for catecholamine synthesis in adrenal medulla [36]. In addition, the maternal

week foetuses' cord blood and 70 ng/mL at the end of gestation [16, 21].

of the foetal area is observed [3, 35].

74 Umbilical Cord Blood Banking for Clinical Application and Regenerative Medicine

teroid dehydrogenase (11-HSD) [16].

mones levels increase at the end of pregnancy.

catecholamines can go across the placenta [16].

**adrenal gland**

Glucose is recognized as the major energy porter of human metabolism [37–39]. Glycaemia is determined by carbohydrate intake and absorption, by the glycolysis and gluconeogenesis. **Figure 3** summarizes an integrated hormonal mechanism contributing to glycaemia balance. When glycaemia is reduced, mechanisms are produced to avoid hypoglycaemic shock, inducing appetite and compensatory mechanisms, as the lack of stimulation by β-cell to produce insulin and the stimulation of glucagon by α-2 pancreatic cells. When glycaemia increases, insulin promotes the intracellular cross of glucose through expression of receptors and carriers. In addition, a general enzyme activity occurs in liver, skeletal muscle, adipose tissue, etc., increasing the protein synthesis, lipogenesis and glycogenesis [25].

**Figure 3.** Integrative scheme of hormone response to hypoglycaemia and hyperglycaemia. ACTH, adrenocorticotropic hormone, GH, growth hormone. Red lines, inhibition; green lines, activation; Dot white lines, no effect. Red lines bearing a cross: missing the inhibitory mechanism; green lines bearing a cross: missing the stimulating mechanism. Modified from Sibernagl and Despopoulos [25] and Nelson and Cox [26].

Hypoglycaemia and a high level of amino acids are two major stimuli for glucagon release. However, fasting, general adrenergic excitation and a decrease in the fatty acid concentrations also lead to glucagon release. On the other hand, hyperglycaemia inhibits glucagon release. The main role of glucagon is raising the glycaemia [24] by increasing glycogenolysis (that is intensified by an increased lipolysis) and diminishing glycolysis. Somatostatin is secreted by the α-cells of the pancreas and inhibits GH, thyroid-stimulating hormone (TSH), gastrin, insulin and glucagon release. All these effects result in a hypoglycaemic action. Glycaemia is registered by glycoreceptors inducing compensation by modifying insulin and glucagon release. Nevertheless, this action is completed by cortisol action and the effect of catecholamines (**Figure 3**).
