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Biomedical subjects

W A McKinley

Publications and source records attributed to W A McKinley.

7 recordsLinked to original sources

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↗

Structure activity studies on somatostatin.

Seven synthetic analogues of somatostatin helped clarify structural requirements for suppression of growth hormone secretion in rats. Size of the ring is not critical; deletions of serine-13, lysine-4 or asparagine-5 result in peptides which retain an appreciable fraction of the activity. The analogue des-Ala1, Gly2, Asn5-somatostatin lowers plasma growth hormone and insulin levels without affecting plasma glucagon levels significantly.

Amino Acid Sequence↗

Luteinizing hormone-releasing hormone. Antiovulatory activity of analogs substituted in positions 2 and 6.

Ten analogs of luteinizing hormone-releasing hormone (LH-RH) substituted in position 2 with D-amino acids and at 6 with either a D-amino acid or a nonasymmetric amino acid were synthesized by solid-phase methodology and assayed for antiovulatory activity. [D-Phe2]-LH-RH substituted in the 6 position with D-Ala, D-Leu, D-Arg, D-(Ph)Gly, D-Phe, or 2-Me-Ala possessed varying degrees of antiovulatory activity. [D-p-F-Phe2-D-Ala6]-LH-RH was one of the most active antiovulatory compounds, while the [D-p-Cl-Phe2-D-Ala6]-LH-RH analog was devoid of activity at a comparable dose.

Animals↗