The testes and ovaries (gonads) synthesize hormones necessary for sexual differentiation and reproduction. A single hypothalamic-releasing factor, gonadotropin-releasing hormone, stimulates the anterior pituitary to release the glycoproteins luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Like ACTH, LH and FSH bind to surface receptors and cause an increase in cAMP. LH stimulates the testes to produce testosterone and the ovaries to produce estrogens and progesterone (see Fig. 18.27). FSH regulates the growth of ovarian follicles and stimulates testicular spermatogenesis.
D. Mechanism
Each steroid hormone diffuses across the plasma membrane of its target cell and binds to a specific cytosolic or nuclear receptor. These receptor–ligand complexes accumulate in the nucleus, dimerize, and bind to specific regulatory DNA sequences (hormone response elements [HRE]) in association with coactivator proteins, thereby causing increased transcription of targeted genes (Fig. 18.28). An HRE is found in the promoter or an enhancer element (see p. 440) for genes that respond to a specific steroid hormone, thus insuring coordinated regulation of these genes. Hormone–receptor complexes can also inhibit transcription in association with corepressors. [Note: The binding of a hormone to its receptor causes a conformational change in the receptor that uncovers its DNA-binding domain, allowing the complex to interact through a zinc finger motif with the appropriate DNA sequence. Receptors for the steroid hormones, plus those for thyroid hormone, retinoic acid (see p. 386), and 1,25-dihydroxycholecalciferol (vitamin D; see p. 390), are members of a superfamily of structurally related gene regulators that function in a similar way.]
E. Further metabolism
Steroid hormones are generally converted into inactive metabolic excretion products in the liver. Reactions include reduction of unsaturated bonds and the introduction of additional hydroxyl groups. The resulting structures are made more soluble by conjugation with glucuronic acid or sulfate (from 3′phosphoadenosyl-5′-phosphosulfate; see p. 162). These conjugated metabolites are fairly water soluble and do not need protein carriers. They are eliminated in feces and urine.
VIII. CHAPTER SUMMARY