**5.5 Adrenal hormones**

10 Steroids – Basic Science

ACTH stimulated corticosterone production by cells of the fasciculate-reticular zone or the basal and agonist-stimulated aldosterone secretion of dispersed cells from the glomerulosa zone. The ACTH-receptor antagonist corticotropin-inhibiting peptide blocks the secretion of corticosterone induced by ACTH to cells from the fasciculate-reticular zone, but does not modify orexins effects. Both orexins enhance cyclic-AMP release by cells in the fasciculatereticular zone. The selective inhibitor capacity of protein-kinase A (PKA) H-89 decreased corticosterone responses to both ACTH and orexins. A subcutaneous injection of orexin A and B evokes a clear-cut increase in the plasma concentration of corticosterone, but not of aldosterone. The effect of orexin-A on corticosterone release is higher than the effect of orexin-B. Based on these results the authors suggest that orexins exert a selective and direct glucocorticoid secretagogue action on the adrenals of the rat, acting through a receptormediated activation of the adenylate cyclase/PKA-dependent signaling pathway

Stimulating orexin receptors results in higher ACTH secretion by the pituitary and has a direct stimulatory effect on adrenocortical cells (Malendowicz et al., 1999; Spinazzi et al.,

Galanin is a 29- or 30- amino acid long neuropeptide expressed in the brain, spinal cord, and gut that acts via three subtypes of G protein-coupled receptors. Galanin increases the basal secretion of cortisol from dispersed inner adrenocortical cells, without affecting the effects of ACTH (Belloni et al., 2007). Galanin stimulates the release of corticotrophin releasing hormone (CRH) and ACTH, enhances glucocorticoid secretion by the adrenal cortex, and directly stimulates corticosterone secretion from the adrenals through GAL-R1 and GAL-R2 receptors and the release of noradrenaline from the adrenal medulla. Other results suggest that galanin increases corticosterone release via an indirect paracrine mechanism involving the local release of catecholamines, which in turn activates beta-adrenoceptors located on

The VIP and neuropeptide Y (NPY) are the most abundant transmitter-peptides in the adrenal gland (Whitworth et al., 2003). These peptides act as neurotransmitters and exert endocrine, paracrine or autocrine effects in numerous cell types, particularly in the adrenals and ovaries. *In vitro*, the adrenal responsiveness to VIP depends on the model used: in rats, VIP stimulates aldosterone production by the adrenal capsular tissue (Cunningham & Holzwarth, 1988) and by intact perfused adrenal glands (Hinson et al., 1992), but not by dispersed zona glomerulosa cells (Enyedi et al., 1983; Hinson et al., 1992). There is evidence that VIP acts on chromaffin cells present beneath the adrenal capsule, stimulating the release of catecholamines, which in turn stimulate aldosterone secretion (Whitworth et al., 2003). It seems that the mechanisms used by NPY in the adrenals are the same as those used by VIP

The pituitary adenylate-cyclase activating polypeptide (PACAP) and its receptors are present in the central nervous system (CNS), the testicles, adrenals, and ovaries. LH increases PACAP mRNA levels in pre-ovulatory follicles, and stimulates estrogen and

(Malendowicz et al., 1999).

2006; Kagerer & Jöhren 2010).

adrenocortical cells (Tortorella et al., 2007).

**5.4.3 Vasoactive intestinal peptide and neuropeptide Y** 

**5.4.4 Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP)** 

**5.4.2 Galanin** 

(Renshaw et al., 2000).

The adrenals secrete steroid hormones, catecholamines and peptidergic hormones. Evidence suggests that almost all the adrenal hormones play a role on their own regulatory process.
