FSH

Two protein hormones, inhibin and activin, have been identified in gonadal tissue. Inhibin has been isolated from ovarian foUicular fluid and found to inhibit pituitary secretion of FSH. Inhibin is a glyocoprotein heterodimer consisting of two disulfide-linked subunits, a and P two types of P-subunit,... 

P and Pg, exist in foUicular fluid. Control of inhibin secretion involves a feedback relationship in which circulating FSH stimulates inhibin secretion, which in turn reduces the secretion of FSH (8). Both the homo- and the heterodimers of the P-subunits of inhibin promote the secretion of FSH and thus have been termed activins. Activin is secreted by the ovary and the testes into the circulation. In addition, both inhibin and activin have intragonadal autocrine and paracrine effects that influence gonadal steroidogenesis (9). 

Fig. 3. Fluman LH, FSH, and TSH a suburnt [69431-84-1]. Amino acid numbering is relative to maximum homology between species (48). Note the 4 amino acid deletion in human a suburnt between positions 6 and 9. Consensus glycosylation sites are at Asn-56 and 82. GHO = carbohydrate chain.

One glycosylation site exists on the P suburhts of human LH [53664-53-2 and TSH [64365-92-OJ ie, Asn-30 (Fig. 4). In some species, Asn-13 of LH-P is glycosylated (48). FSH-P suburnt [58857-12-8] is glycosylated at two sites, Asn-13 and 30. Based on interactions of synthetic peptides with the LH receptor, loops formed by P93—100 and P38—57 may be essential for hormone bioactivity (48). Highly conserved sequences between residues 31—37 have been implicated in the formation of the a—P suburnt dimer (48), which is absolutely necessary for the expression of bioactivity. 

Fig. 4. Human LH, FSH, and TSH P subunits. Amino acid numbeiing is relative to maximum homology between the three subunits. Consensus...

Fig. 4. FSH receptor-binding potencies of equine FSH ( ), eCG purified from pregnant mate s semm (O), and endometrial cups (A). Receptor-binding in ceU membrane fractions, B/Bq from (a) horse, (b) calf, and (c) rodent testes (40). Courtesy of Butterworth-Heinemaim.

Inhibin and Activin. Inhibin, a water-soluble, gonadal factor known for over 50 years to inhibit pituitary function, has been isolated and identified (127—130). Inhibin is a glycoprotein hormone that preferentially inhibits the secretion of FSH. It consists of an a-chain subunit, mol wt 14,000, linked by disulfide bonds to a P-chain subunit, mol wt 18,000. There exist two forms of the P-chain subunit, P-A and P-B. The smaller subunit combines with either the P-A or P-B subunit to form inhibin-A or inhibin-B, respectively. 

During the isolation of inhibin from foUicular fluid, some chromatographic fractions stimulated FSH release from cultured anterior pituitary cells, suggesting the existence of FSH releasing proteins (FRPs). Two FRPs, given the generic term activins, were subsequentiy isolated (131,132). One is composed of two disulfide-finked P-A subunits (activin A) the other consists of similarly finked P-A and P-B subunits (activin AB). 

Studies confirm that inhibin plays a role in regulating FSH secretion. However, the importance of this role in the human has not yet been determined. If inhibin-regulated FSH secretion is pivotal in foUicular recmitment and growth, then it may be possible to block ovulation by means of inhibin antagonists. 

Follicle Stimulating Hormone (FSH, foilitropin) [9002-68-0] Mr 36,000. Purified by Sephadex GlOO gel filtration followed by carboxymethyl-cellulose with NH4OAC pH 5.5. The latter separates luteinising hormone from FSH. Solubility in H2O is 0.5%. It has an isoelectric point of 4.5. A soln of Img in saline (lOOmL) can be kept at 60° for 0.5h. Activity is retained in a soln at pH 7-8 for 0.5h at 75°. The activity of a 50% aq EtOH soln is destroyed at 60° in 15 min. [Bloomfield et al. Biochim Biophys Acta 533 371 1978 Hartree Biochem J100 754 1966 Pierce and Parsons Ann Rev Biochem 50 465 1981.]... 

Figure 13.29. Simaurc til Ph ShF-. -.hoiAing poKmonc chAin-, til apex-shared pseudo trigonal hipvrattiidal u (Pli FSh F ...

In premenopausal women the ovary is the richest source of aromatase and hence estrogen. Aromatase is confined to the granulosa cells and is produced under the influence of gonadotropins (FSH and LH). Despite being a rich source of aromatase, three separate studies have shown that aromatase inhibitors are unable to sufficiently suppress ovarian estrogen production to postmenopausal levels. One explanation for this phenomenon may be a compensatory rise in gonadotrophins which maintains adequate estrogen production, despite the presence of the inhibitor. As such aromatase inhibitors cannot be used in premenopausal breast cancer patients. After menopause, ovarian... 

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