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A Corbin

Publications and source records attributed to A Corbin.

At least 37 records · Page 2Linked to original sources
PubMed1984

Cyclic response of hypophysectomized rats to ovulation induced by LHRH agonist: mediation by prostaglandins.

Further confirmation that the LHRH/LHRH agonist-induced ovulation in the hypophysectomized (hypx) rat is due to a direct ovarian effect and not mediated by LH release from residual pituitary tissue or other CNS sites is provided by the persistence of this effect despite concomitant median eminence lesion or passive immunization to LH. Adrenalectomy did not affect the ovulatory activity of the LHRH agonist, D-Trp6-N alpha MeLeu7-DesGly10-Pro9-NHEt-LHRH (Wy-40,972), in the hypx rat. Prior administration of a potent LHRH antagonist blocked ovulation induced in hypx proestrous rats by Wy-40,972 but not by LH-S19. Ovulation can be induced by Wy-40,972 one day earlier (e.g. metestrus) in the intact rat than it can in the hypx rat. Results in the hypx metestrous rat indicate that the ovulatory responsiveness of the intact rat at this stage of the cycle may occur by complementary action of Wy-40,972-stimulated endogenous LH release and a direct ovarian effect of the agonist. Prostaglandins (PG) are involved in the ovulatory mechanism of Wy-40,972 in the hypx proestrous rat as evidenced by the dose-dependent inhibition of this effect by PG synthetase inhibitors, indomethacin and Fentiazac. Moreover, there were significant increases in ovarian concentrations of PGF2 alpha and PGE2-PGE1 in response to Wy-40,972 that could be prevented by indomethacin. However, exogenous administration of either of these PG's was not effective in inducing ovulation in the hypx rat.

Acetates↗
PubMed1984

[Not Available].

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France↗
PubMed1983

[Not Available].

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France↗
PubMed1982

Resistance of the mouse to the antifertility effects of LHRH agonists.

In the mouse, the LH-releasing activity of the LHRH agonist, D-Trp6-N alpha-MeLeu7-DesGly10-Pro9-NHEt-LHRH (Wy-40,972), was established by its ability both to induce ovulation when administered at 1600 hours on the the second day of diestrus and to elevate serum LH in adult males. While Wy-40,972 was only slightly less active in terms of these and points than it was in the rat, the predictive and possibly causal association between LH-releasing and antifertility activity established for this LHRH analog in the rat could not be clearly identified in the mouse. A total daily dose of 1000 microgram Wy-40,972/mouse was required to completely inhibit pregnancy during days 1-7 of pregnancy and produced only partial inhibition during days 7-12. This dose represents, on a body weigh basis, 8250 times the 100 percent effective pregnancy-terminating dose for the rat during equivalent intervals. The resistance of the mouse to the antifertility activity of Wy-40,972 was found not to be restricted to this particular LHRH analog or to the reproductive state. Administration of another potent LHRH analog, D-Ala6-DesGly10-Pro9-NHEt-LHRH (Wy-18,481), to adult male mice at a dose of 100 microgram/mouse/day for up to 14 days had no inhibitory effect on the weights of the testes or sex accesory organs. This dose of Wy-18,481 is 7500 times that necessary for significant reduction of these reproductive organ weights in rats within 7 days of treatment. Investigation as to the nature of the mouse's apparently divergent response to the LHRH agonists may further elucidate the antifertility mechanism of such compounds in susceptible species.

Animals↗
PubMed1981

[Not Available].

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Genetics↗
PubMed1980

Luteinising hormone-releasing and anti-fertility properties of a glucagon-selective somatostatin analogue.

The hypothalamic tetradecapeptide, somatostatin (SRIF), inhibits the secretion of growth hormone (GH) and numerous other hormones, including insulin and glucagon. Attempts to use SRIF as an adjunct in the treatment of diabetes mellitus met with limited success due to its short biological half-life and the undesirable diabetogenic activity of its insulin-lowering properties. Efforts at synthesis have yielded SRIF derivatives with prolonged GH-lowering activity which did not suppress glucagon or had equivalent insulin-inhibiting activity as well as several short-acting compounds with the appropriate glucagon specificity. A dodecapeptide analogue [des-Ala, Gly] His-D-Trp-SRIF (Wy-41, 747) has been identified that combines selective inhibition of GH and glucagon release with prolonged activity. However, in routine pharmacological tests chronic treatment of mature rats with Wy-41, 747 produced anti-reproductive effects resembling those described for luteinising hormone (LH)-releasing hormone (RH) and its agonists. We report here that Wy-41, 747, unlike SRIF and other of its analogues tested, releases LH, induces ovulation and inhibits pregnancy when administered before or after implantation; these properties are traditionally associated with the separate LH-releasing class of peptides.

Animals↗
PubMed1979

Agonist (ovulation induction) and post-coital contraceptive properties of [D-Ala6] and [D-Trp6]-LHRH series.

Seven derivatives of LH-RH, representing the [D-Ala6] or [D-Trp6] series, with or without a Fujino modification, were evaluated for ovulation-inducing (agonist and post-coital contraceptive activity in rats. Six of these analogues had a high degree of agonist and pregnancy-terminating potency. In general, several modifications can result in a particular series of composite molecules that possess a biologic potency greater than each of its predecessors; this correlation of structure with activity was more consistent in the [D-Ala6]-series than in the [D-Trp6]-series. The relationship between structural modifications, resistance to enzyme degradation (based on literature reports) and increased biologic potency is discussed.

Animals↗
PubMed1979

[Not Available].

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Europe↗
PubMed1978

The anti-reproductive pharmacology of LH-RH and agonistic analogues.

LH-RH and three particular ("super") analogues were evaluated for agonistic (ovulation-induction and short-term uterotrophic properties) and postcoital contraceptive activity in rodents. Additionally, LH-RH and/or a representative analogue (D-Ala6-des Gly10-Pro9-LH-RH ethylamide) were tested for postcoital contraceptive/vaginal smear/return to fertility effects, precoital contraceptive activity, and effects on puberty in the immature female. All compounds induced ovulation and uterotrophic effects and terminated pregnancy when administered either pre- or post-implantation. LH-RH and the representative analogue, while terminating pregnancy postcoitally, produced an associated break in the characteristic leucocytic vaginal smear of pregnancy to one of cornification by day 12; at this time mating and insemination were reestablished and all rats carried to normal term. Precoitally, LH-RH administered to nembutalized (but not to unblocked) rats produced a 50% reduction in the pregnancy rate and a 38% decrease in the number of viable pups delivered. In immature rats, the representative analogue delayed puberty (i.e. vaginal canalization) and retarded the growth of the ovaries, uteri, and anterior pituitary gland. The collective data strongly support the concept that LH-RH and agonistic derivatives, in spite of their putative pro-fertility classification, are characteristically antifertility by nature. Since the latter effect appears to be the paradoxically dominant one, it is suggested that LH-RH agonism is synonymous with contraception. Furthermore, such peptides may represent a new potential approach to fertility control.

Animals↗
PubMed1977

Postcoital contraceptive effects of agonist analogs of luteinizing hormone-releasing hormone.

Various analogs of synthetic hypothalamic luteinizing hormone-releasing hormone (LH-RH) were evaluated for agonistic (ovulation-inducing), postcoital contraceptive, and direct uterotrophic activities. All analogs showing agonistic activity also possessed the ability to terminate pregnancy, as did LH-RH; there appeared to be a direct relationship between agonistic and postcoital potency and activity. The highly potent and active LH-RH agonist, D-[Ala]6-des-[Gly]10-pro9-ethylamide-LH-RH, proved to be the most potent and active postcoital preimplantational and postimplantational antifertility agent. In contrast to LH-RH, none of the analogs tested in the hypophysectomized animal produced a uterotrophic effect, revealing a selective extrapituitary effect of the parent hormone. The collective data demonstrate that peptides derived from LH-RH and bearing agonistic properties can terminate pregnancy postcoitally, via disruption of the pituitary-ovarian reproductive complex. Possible mechanisms are discussed, and the use of members of this neurohormonal class as potential profertility agents should be weighed with caution.

Animals↗