RESUMO
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.
Assuntos
Anticoncepcionais Hormonais Pós-Coito , Anticoncepcionais Pós-Coito , Hormônio Liberador de Gonadotropina/análogos & derivados , Hormônio Liberador de Gonadotropina/farmacologia , Prenhez/efeitos dos fármacos , Animais , Implantação do Embrião/efeitos dos fármacos , Feminino , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Hormônios/farmacologia , Hipofisectomia , Gravidez , RatosRESUMO
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.
Assuntos
Somatostatina/análogos & derivados , Sequência de Aminoácidos , Animais , Glucagon/sangue , Hormônio do Crescimento/sangue , Insulina/sangue , Métodos , Ratos , Somatostatina/síntese química , Somatostatina/farmacologia , Relação Estrutura-AtividadeRESUMO
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.
