**5.2.1 Leptin**

Leptin is a hormone secreted by the adipose tissue, and its participation in the regulation of steroid hormones is controversial. *In vitro* studies show that the participation of leptin in the regulation of steroid hormones release depends on the species studied. In avian ovarian cells leptin stimulates the release of progesterone and estradiol, blocks testosterone secretion, and does not affect arginine-vasotocin secretion (Sirotkin & Grossmann 2007). In granulosa cells from rats, high leptin concentrations inhibits the stimulatory effects of insulin-like growth factor I (IGF-I) on FSH-stimulated estradiol secretion, but does not affect progesterone secretion (Zachow and Magoffin, 1997; Duggal et al., 2002; Ricci et al., 2006). In cultured granulosa cells leptin also suppresses the stimulating effect of the transforming growth factor β (TGF-β) on FSH-dependent estrone and estradiol secretion, as well as in aromatase mRNA expression and aromatase activity (Zachow et al., 1999).

Leptin inhibits insulin-induced estradiol secretion by granulosa cells and decreases the insulin-induced increases of progesterone production in bovine granulosa cells (Spicer & Francisco, 1997). Co-stimulated by FSH and dexamethasone, leptin blocks steroid hormone synthesis by the ovaries and the synthesis of pregnenolone, progesterone, and 20alphahydroxy-4-pregnen-3-one. Leptin also reduces the expression of adrenodoxin, an enzyme in the P50scc electron transport system (Barkan et al., 1999), and inhibits the synthesis of insulin-stimulated progesterone production from human luteinized granulosa cells (Brannian et al., 1999). The synthesis of functional leptin receptors depends on pituitary hormones, since hypophysectomized rat theca cells do not have such receptors (Zachow et al., 1999).

Studies in human granulosa cells suggest that *in vitro* the effects of leptin on the secretion of estradiol and progesterone depend on the doses used; with low doses of leptin having a stimulatory effect and high doses an inhibitory effect (Karamouti et al., 2009). Leptin and leptin fragments enhance the secretory activity of aldosterone and corticosterone by the adrenal cortex of rats (Malendowicz et al., 2003; Markowska et al., 2004). However, later studies by Malendowicz et al., (2007) reported that leptin inhibits steroid-hormone secretion from the adrenal cortex by lowering the response to stress of the hypothalamic-pituitaryadrenal (HPA) axis and by increasing the release of catecholamines from the adrenal medulla. Because leptin Ob-receptor is expressed in the adrenal gland, it seems that leptin modulates adrenal hormones secretion by acting as a circulating hormone (Malendowicz et al., 2007). Leptin blocks the ovarian steroid synthesis co-stimulated by FSH and dexamethasone. *In vitro* studies show that leptin inhibited the secretion of pregnenolone, progesterone, and 20alpha-hydroxy-4-pregnen-3-one, as well as the secretion of progesterone induced by the co-stimulation by forskolin and dexametasene; without modifying the forskolin induction of cAMP (Barkan et al., 1999).
