Mechanisms of reproductive deficiency in male rats treated neonatally with a gonadotrophin-releasing hormone antagonist

J Endocrinol. 1994 Sep;142(3):517-25. doi: 10.1677/joe.0.1420517.

Abstract

It is well known that males injected neonatally with oestradiol or antiserum or antagonists (ANT) against gonadotrophin-releasing hormone (GnRH) show multiple reproductive disorders. In the present work, in males treated neonatally with GnRH-ANT, we have analysed: (1) whether the impairment of reproductive function can be blocked by simultaneous treatment with gonadotrophins, (2) the possible differences in the effects of GnRH-ANT injected before or after the proliferation of Sertoli cells which takes place between days 1 and 15 of age, and (3) the mechanism(s) for the increased FSH secretion observed in adulthood. Experimental designs included: administration of GnRH-ANT between days 1 and 16 or 15 and 30 of age, simultaneous administration of gonadotrophins and GnRH-ANT to neonatal males, and measurement of FSH secretion after orchidectomy or specific destruction of Leydig cells with ethylene dimethane sulphonate (EDS) in adult males treated neonatally with GnRH-ANT. The principal new data presented in our studies are the following: (1) delayed puberty was observed not only in males injected neonatally with GnRH-ANT, but also in those injected with gonadotrophins or with GnRH-ANT and gonadotrophins, (2) the decreased fertility and increased FSH secretion observed in adult males treated neonatally with GnRH-ANT were normalized by simultaneous administration of GnRH-ANT and gonadotrophins, and (3) the increased FSH secretion in adult males treated neonatally with GnRH-ANT remained after EDS or orchidectomy, suggesting that mechanisms other than decreased inhibin secretion were involved in the increased secretion of FSH.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Fertility / drug effects*
  • Follicle Stimulating Hormone / metabolism*
  • Follicle Stimulating Hormone / pharmacology
  • Gonadotropin-Releasing Hormone / analogs & derivatives*
  • Gonadotropin-Releasing Hormone / antagonists & inhibitors*
  • Gonadotropin-Releasing Hormone / pharmacology
  • Leydig Cells / drug effects
  • Luteinizing Hormone / pharmacology
  • Male
  • Mesylates / pharmacology
  • Orchiectomy
  • Rats
  • Rats, Wistar
  • Sexual Maturation / drug effects*

Substances

  • Mesylates
  • Gonadotropin-Releasing Hormone
  • LHRH, N-acetyl-(4-chlorophenylalanyl)(1)-(4-chlorophenylalanyl)(2)-tryptophyl(3)-arginyl(6)-alanine(10)-
  • Luteinizing Hormone
  • Follicle Stimulating Hormone
  • ethylene dimethanesulfonate