Biosynthesis of steroid hormones de novo

FSH and LH function to regulate gonadal steroid hormone biosynthesis and initiate and maintain germ cell development in concert with peripheral hormones and paracrine soluble factors. The four heterodimeric glycoprotein hormones—LH, FSH, TSH, and hCG—share structural homology, having evolved from a common ancestral gene. Although both the homologous LH and FSH molecules are cosecreted by gonadotrophs, their regulatory mechanisms are not uniformly concordant. The αGSU, LHβ, and FSHβ subunits are encoded by different genes, located on chromosomes 6, 11, and 19, respectively ( Fig. 8-30 ; see also Fig. 8-2 ). The heterodimeric structure of the common—and unique—subunit of LH and FSH is essential for biologic activity. Disulfide linkages within each subunit result in a tertiary structure that enables and maintains noncovalent heterodimerization, which also determines the ultrastucture of the mature folded molecule to facilitate specific ligand-receptor interaction. 402 Glycosylation of the subunits occurs by the transfer of oligosaccharide complexes to asparaginylasparagine residues. 403 Post-translational processing of carbohydrate side chains is critical for hormone signaling and may be species specific, distinct for LH and FSH, and may even vary physiologically to influence biologic activity and metabolic clearance rates. 403,404 The human LH/CG β gene cluster comprises seven genes, arising from gene duplication, of which one gene encodes LHβ, one encodes CGβ, and the remainder are pseudogenes. Unlike LH, hCG is present only in primate and equine species and is expressed primarily in the placenta. The LHβ and CGβ genes have different promoters and transcriptional start sites, accounting for their different tissue distribution patterns of expression. 405 LHβ includes a 24–amino acid signal peptide followed by a 121–amino acid mature protein. In contrast, the mature hCGβ protein is 145 amino acids in length and does not include a leader peptide, but contains a 24–amino acid C-terminal extension important for the longer biologic half-life of hCG. 406,407 The FSHβ gene, on chromosome 11, is organized similarly to the other glycoprotein hormone β genes, encoding a mature peptide of 111 amino acids, with two glycosylation sites, and like LHβ, it is expressed only in gonadotrophs.

Progestins , the most important of which is progesterone , are the other type of female sex hormone and are named for their role in maintaining pregnancy (pro- gestation ). Estrogens and progestins are secreted cyclically during menstruation . During the menstrual cycle , the ruptured ovarian follicle (the corpus luteum ) of the ovary produces progesterone, which renders the uterine lining receptive to the implantation of a fertilized ovum . Should this occur, the placenta becomes the main source of progesterone, without which the pregnancy would terminate. As pregnancy progresses, placental production of progesterone increases, and these high doses suppress ovulation , preventing a second conception . The contraceptive quality of progesterone led to the development of structurally modified progestins and estrogens—the oral contraceptives known as birth-control pills, used by women to prevent unwanted pregnancy.

Biosynthesis of steroid hormones de novo

biosynthesis of steroid hormones de novo

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