Postcoital Contraceptive Effects Of Agonist Analogs Of Luteinizing Hormone-Releasing Hormone

Corbin, Alan; Beattie, Craig W.; Rees, R. W.; Yardley, J. P.; Foell, Theodore; Chai, Sie Y.; Mcgregor, Herbert; Garsky, Victor M.; Sarantakis, Dimitri; McKinley, W. A.

doi:10.1016/s0015-0282(16)42500-8

Cited by 41 publications

(5 citation statements)

References 17 publications

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“…Thus, while LRF isolated from the hypothalamus possesses the ability to stimulate the secretion of both LH and FSH from the pituitary gland, chronic treatment with this peptide inhibits, to a great extent, many aspects of reproductive performance. Similar effects of LRF were confirmed with long acting, more GONADOCRININS 1207 potent agonistic analogs (super LRFs) (15)(16)(17)(18)(19).…”

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confidence: 62%

Gonadocrinins: Peptides in Ovarian Follicular Fluid Stimulating the Secretion of Pituitary Gonadotropins*

et al. 1981

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A newly discovered small peptide purified from rat follicular fluid stimulates the pituitary to release FSH and LH in vitro as well as in vivo. Dialysates of crude acid extracts of ovarian follicular tissue and fluid from rats pretreated with PMS gonadotropin stimulate the secretion of both LH and FSH, but not PRL, GH, or TSH, in a pituitary monolayer culture system. This stimulating factor, named gonadocrinin for operational facility, is smaller than 3500 daltons; its biological activity disappears after treatment with trypsin. Gonadocrinin is not recognized by two-antisera binding the decapeptide LRF even though D-Phe2,D-Trp6-LR, an LRF analog antagonist, competitively inhibits the activity of ovarian gonadocrinin. Cultured rat granulosa cells also secret substances with gonadocrinin activity in vitro, indicating that the granulosa cells probably are in vivo the source of gonadocrinin. A crude preparation of gonadocrinin given iv to rats on the second day of diestrus induced secretion of LH comparable to that produced by a 250-ng LRF injection. Gonadocrinin has chemical characteristics different from those of LRF. When purified gonadocrinin or LRF was applied to an identical isocratic high pressure liquid chromatography system, LRF was eluted at a position different from that of gonadocrinin, indicating that, chemically, gonadocrinin is not identical to the hypothalamic decapeptide, LRF.

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confidence: 62%

Gonadocrinins: Peptides in Ovarian Follicular Fluid Stimulating the Secretion of Pituitary Gonadotropins*

et al. 1981

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“…Although GnRH and its analogs were initially expected to be valuable for the induction of ovulation, it has become apparent that these compounds exert marked antifertility effects in both male and female animals (18,19). In female rats, GnRH analogs inhibit implantation (20,21), cause termination of pregnancy (20,22), and inhibit sexual development (23).…”

Section: Discussionmentioning

confidence: 99%

Ovarian Gonadotropin-Releasing Hormone Receptors, II. Regulation and Effects on Ovarian Development

et al. 1980

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The direct antagonistic actions of gonadotropinreleasing hormone (GnRH) and its agonist analogs on hormonal (hCG and epinephrine) activation of progesterone and cAMP production in isolated luteal cells were described in the preceding paper. These effects are mediated by specific, high affinity GnRH receptors demonstrated in both ovarian membranes and isolated luteal cells. The present studies show that the administration of GnRH agonist analogs in vivo markedly inhibits PMS gonadotropin (PMSG)-induced follicular development and the increased formation of LH receptors after hCG-induced luteinization. Three GnRH agonist analogs with structural modifications at positions 6 and 10 given by osmotic minipump infusion, caused complete inhibition of the trophic actions of both gonadotropins. An antagonist analog which binds to the ovarian GnRH receptor with high affinity did not inhibit the gonadotropin-induced changes.Using the PMSG/hCG-primed immature rat, the effects of a single injection of GnRH were studied and compared to the action of hCG. Whereas the latter caused a marked loss of GnRH and LH receptors, GnRH caused a loss of ovarian LH receptors but a consistent increase in ovarian GnRH receptors; PRL receptors also showed a transient decline, and there was a fall in serum progesterone. In hypophysectomized rats, GnRH and hCG similarly caused a decrease in ovarian LH receptors and a transient change in the PRL receptor concentration. The GnRHinduced decrease in LH and PRL receptors in hypophysectomized animals indicates that GnRH analogs can act directly on the ovary and that their effects are not only due to the secondary release of gonadotropins from the pituitary gland. The direct inhibitory actions of this class of GnRH peptides upon gonadal function constitutes an important component of the antifertility effects of these compounds. (Endocrinology 107: 414, 1980). G ONADAL receptor sites for GnRH, 1 recently identified in the luteinized rat ovary (1) and characterized in the preceding paper (2), are responsible for mediating the direct inhibitory effects of GnRH agonists on ovarian function (3-6). Such direct ovarian effects of GnRH agonists, together with indirect actions exerted via gonadal desensitization by elevation of endogenous gonadotropins (7, 8) and pituitary refractoriness (9, 10), are responsible for the marked inhibitory effects of GnRH peptides upon reproductive function. The demonstration that GnRH agonists inhibit FSH-induced steroidogenesis in cultured granulosa cells (5) suggests that GnRH receptors are also present in ovarian follicles and are retained during subsequent luteinization. It was therefore of interest to determine whether the immature ovary contained GnRH receptors before gonadotropin priming and to correlate these sites with the ability of GnRH to antagonize the effects of exogenous PMS gonadotropin (PMSG) and hCG on ovarian development.

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“…In the intact female, ovulation and ovum implantation are delayed, pregnancy is terminated, and sexual maturation is delayed (123)(124)(125)(126)(127)(128)(129)(130)(131). In the intact male, effects include disruption of spermatogenesis, atrophy of secondary sex organs, and reduced testosterone biosynthesis (132)(133)(134)(135)(136)(137)(138)(139)(140).…”

Section: ) Backgroundmentioning

confidence: 99%

Gonadotropin-Releasing Hormone Receptors: Characterization, Physiological Regulation, and Relationship to Reproductive Function

1981

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Postcoital Contraceptive Effects Of Agonist Analogs Of Luteinizing Hormone-Releasing Hormone

Cited by 41 publications

References 17 publications

Gonadocrinins: Peptides in Ovarian Follicular Fluid Stimulating the Secretion of Pituitary Gonadotropins*

Gonadocrinins: Peptides in Ovarian Follicular Fluid Stimulating the Secretion of Pituitary Gonadotropins*

Ovarian Gonadotropin-Releasing Hormone Receptors, II. Regulation and Effects on Ovarian Development

Gonadotropin-Releasing Hormone Receptors: Characterization, Physiological Regulation, and Relationship to Reproductive Function

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