**5. Hormonal signals**

6 Steroids – Basic Science

gonads. The expression of 3β-HSDs is enhanced by ACTH and LH. These isomerases catalyze the formation of Δ4-3-ketosteroids from A5-3β-hydroxysteroids, an obligate step in the biosynthesis of progestins, androgens, estrogens, mineralocorticoids and glucocorticoids. 3β-HSDs catalyze the dehydrogenation of the 3B-equatorial hydroxyl group and the subsequent isomerization of the olefinic bond to yield the A4 3-ketone structure; converting pregnenolone into progesterone, l7α-hydroxypregnenolone into 17α-

Protein kinase A signaling activators (forskolin, dibutyrylcAMP) increase the synthesis of dehydroepiandrosterone and A4, as well as the levels of 3β-HSD and P-450c17 mRNA transcripts. Activation of the protein kinase C pathway by phorbol ester treatment also elevates 3β-HSD mRNA levels and lowers P-450cl17 mRNA levels (Auchus & Miller. 2000).

The 17 -Hydroxylase/17,2O-Desmolase (P-45Oc7f or CYP17A1 lTl) is a cytochrome P450 enzyme with 17-hydroxylase and 17,20-lyase activities that catalyzes two reactions: the hydroxylation of pregnenolone and progesterone at carbon 17, and the conversion of pregnenolone into C-19 steroids. P-450c17 is a key enzyme in the steroidogenic pathway producing all steroid hormones (progestins, mineralocorticoids, glucocorticoids, androgens, and estrogens). The theca cells of the follicle and the theca lutein cells of the corpus luteum, as well as the ovarian stroma, the adrenal gland, and Leydig cells express P-450c17. (Auchus

Aromatase cytochrome P-450 c17 is an enzyme found in the endoplasmic reticulum membrane that acts on aromatizable androgen. Aromatase P 450 catalyses the biosynthesis of all estrogens from androgens by transforming the A-ring of steroids to an aromatic state through the oxidation and elimination of the C19 methyl group (Ghosh et al., 2009; Straus & Hsueh, 2000). Aromatase expression is present in fetal and immature ovaries, and in rodents, aromatase expression/activity is restricted to the gonads and the brain. In humans, aromatase activity is expressed by the adrenal medulla (Belgorosky et al., 2008), adipose

FSH is the main factor inducing aromatase activity in mural granulosa cells located on the outer edge of healthy large antral follicles and luteal cells. Aromatase is not expressed in cumulus granulosa cells. The stimulatory effects of FSH are modulated in an inhibitory way by glucocorticoids, prolactin, progestins, inhibin, triiodothyronine and thyroxine (T3-T4) (Chen et

Bone morphogenetic protein 15 (BMP-15) and growth differentiating factor 9 (GDF9) produced by the oocytes also stimulate aromatase expression and the stimulatory effects of the tumor necrosis factor- (TNF-), epidermal growth factor (EGF), transferrin, nitric oxide (NO), and superoxide dismutase (Stocco 2008). Leptin has stimulatory or inhibitory effects on

Acting as an autocrine signal, estradiol enhances the stimulatory effects of FSH on aromatase activity in granulosa cells, and its effects are mediated by the activation of

Androgens enhance FSH effects on aromatase expression by increasing cAMP levels. Aromatizable androgens synthesized by theca-internal cells are the substrate for estrogen

al., 2010). Transforming growth factor-β (TGF-β) enhances FSH effects (Stocco, 2008).

aromatase expression depending on the animal studied (Sirotkin & Grossman, 2007).

hydroxyprogesterone, and dehydroepiandrosterone into A4.

tissue, breast, skin, and bone (Czajka-Oraniec & Simpson, 2010).

**4.3 17 -Hydroxylase/17,2O-Desmolase** 

& Miller, 2000; Straus & Hsue, 2000).

**4.4 Aromatase cytochrome P-450c17** 

estrogen receptor β (Wang et al., 2010).

The regulation of steroid hormones synthesis is mediated by hormones secreted by the pituitary, thyroid, adipose tissue, neuropeptides, adrenals, ovaries and testicles.
