**5.4 Neuropeptides**

The term neuropeptide refers to polypeptidic molecules synthesized and released by neurons that can act neurotransmitters and/or hormones. Common neuropeptides include orexins (A & B) and galanin.

### **5.4.1 Orexins**

Orexin-A and orexin-B (hypocretin-1 and -2) are two neuropeptides produced by neurones located in the lateral hypothalamus. Orexins A and B bind to two different receptors that are coupled to G proteins. Both neuropeptides raise basal corticosterone secretion by dispersed cells obtained from the rat's fasciculate-reticular zone, and do not affect either maximally

Hormonal and Neural Mechanisms Regulating Hormone Steroids Secretion 11

progesterone secretion by granulosa cells stimulated with hCG (Lee et al. 1999). In the adrenals, PACAP stimulates VIP synthesis, which in turn stimulates hormones release (Ait-

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

Endothelins (ETs) are a family of vasoactive peptides secreted by vascular endothelium. ETs play autocrine/paracrine regulatory functions, acting via two subtypes of receptors, ET-A and ET-B. The endocrine cells in the glomerulosa cells of the adrenal cortex express both ET-A and ET-B. The cells of the zone fasciculata/reticularis mainly express ET-B. ETs stimulate the secretion of mineralocorticoids by glomerulosa cells. Its effects on glucocorticoid secretion are lower (Nussdorfer et al., 1997). The effects of ETs on steroidogenic cells are mediated through the activation of various signaling mechanisms, including the stimulation of phospholipase C, phospholipase A2 and adenyl cyclase activity, as well as calcium influx

Noradrenaline (NA) is a cathecolamine secreted by neurons in the adrenal medulla and by chromaffin cells present in the adrenal cortex. In luteal bovine cells NA stimulates progesterone secretion through the beta 1- and beta 2-adrenoceptors. NA also increases cytochrome P-450scc and 3 beta-HSD activity. Prostaglandin F (PGF) inhibits the luteotropic

Human granulosa cells (GCs) express 4 out of 5 dopamine (DA) receptors (D1 and D5 coupled and linked to cAMP increase, D2 and D4; Gi/Gq coupled and linked to IP3/DAG. *In vitro*, the stimulation of human granulosa cells with hCG did not increase mRNA or protein levels of DA receptors. D1 and D2 receptors are also present in the ovaries of rats

The thyroid mainly secretes triyodo tyrosine (T3), tiroxine (T4) and calcitonin. T3 and T4

Rats with hypothyroidism present high progesterone and low testosterone levels, without apparent changes in basal estradiol levels (Hatsuta et al., 2004). Acute experiments with murine Leydig cells, T3 induced StAR expression and progesterone production (Manna et al., 1999). In contrast, chronically stimulating mice Leydig tumor cells with T3 inhibits StAR expression and progesterone production, mainly by decreasing the delivery of cholesterol to the inner mitochondrial membrane (Manna et al., 2001). In cultivated Leydig cells, T3 treatment increased testosterone and estradiol secretions in a dose dependent manner

play several roles in regulating all the mammalian organs and systems.

Ali et al., 2010).

**5.5 Adrenal hormones** 

regulatory process.

**5.5.1 Endothelins** 

**5.5.2 Noradrenaline** 

**5.5.3 Dopamine** 

(Rey-Ares et al., 2007).

**5.6 Thyroid hormones** 

(Maran et al., 2000).

through plasma channels (Delarue et al., 2004).

effect of NA on the luteal tissue (Miszkiel&, Kotwica, 2001).

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 (Malendowicz et al., 1999).

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., 2006; Kagerer & Jöhren 2010).
