Several polypeptide hormones were isolated in pure state from hypothalamic tissue. These hypothalamic hormones stimulate or inhibit the release of pituitary hormones. The determination of their primary structure was followed by large scale synthesis and extensive physiological, clinical and veterinary studies on natural and synthetic hormones as well as their synthetic analogues. The tripeptide (pyro)Glu-His-Pro-NH2 (TRH) stimulates the release of thyrotropin and prolactin in laboratory and domestic animals and humans and can be used clinically for diagnostic tests. The tripeptide Pro-Leu-Gly-NH2 (MIF) inhibits the release of melanocyte stimulating hormone (MSH) in frogs and may have direct effects upon the brain. Further work is needed for the isolation and determinaton of structure of physiological growth hormone releasing hormone, which would be of major clinical value. The structure of prolactin release inhibiting factor (PIF) has not yet been elucidated. The decapeptide (pyro)Glu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2(LH-RH) stimulates the release of both luteinizing hormone (LH) and follicle stimulating hormone (FSH) in rats, hamsters, rabbits, sheep, pigs, cattle, monkeys, chickens and humans, but whether this decapeptide is also the physiological FSH-RH, remains to be established. LH-RH/FSH-RH also stimulates biosynthesis of LH and FSH in rats and induces ovulation in rats, rabbits, hamsters, sheep and women. LH-RH/FSH-RH stimulates spermatogenesis in rats, and based on preliminary results, also in men. Sex steroids appear to be responsible in part for the preferential release of LH and FSH in response to LH-RH/FSH-RH. Examination of the biological properties of a large number of decapeptide analogues of LH-RH/FSH-RH shows that (pyro)Glu, His and Trp residues may be necessary for the release of LH and FSH. Analogues of LH-RH in which other amino acids such as Tyr, Ser, Arg and Leu have been replaced still possess major biological activity, suggesting that these amino acids may be required only for binding to receptors. There has been no dissociation of LH-RH activity from FSH-RH activity in any of the analogues examined. Tripeptide to nonapeptide analogues of LH-RH have little, if any, activity. The synthesis of a competitive analogue of LH-RH/FSH-RH could lead to the development of new methods of birth control. Another such approach could be obtained eventually by the use of antisera to LH-RH.
ASJC Scopus subject areas
- Chemical Engineering(all)