Paradoxical effects of D-Trp6-luteinizing hormone-releasing hormone on the hypothalamic-pituitary-gonadal axis in immature female rats

Fertility and Sterility
J A Vilchez-MartinezA V Schally

Abstract

The effect of administration of a superactive and long-acting analog of luteinizing hormone-releasing hormone (LH-RH), D-Trp6-LH-RH, in doses of 0.05 or 1 microgram/day for 10 days on the hypothalamic-pituitary-gonadal axis was studied in immature female rats. Treatment with a 0.05-microgram dose of analog produced few changes as compared with the control group. Treatment with 1 microgram of D-Trp6-LH-RH did not affect the body weight or the pituitary weight, but increased ovarian weight and decreased uterine weight; elevated serum gonadotropin levels; and lowered the pituitary LH content. This depletion of pituitary LH content was associated with a low pituitary responsiveness to LH-RH. Serum estradiol levels were not modified, suggesting that decreased uterine weight reflects a direct and extrapituitary effect of this analog. The hypothalamic LH-RH content was higher, indicating a possible inhibition of the release of endogenous LH-RH. A delay in vaginal opening was also observed. This indicates that large doses of D-Trp6-LH-RH may interfere with the process of puberty in rats. These findings extend other reports about the paradoxical antifertility effects of large doses of stimulatory analogs of LH-RH.

Citations

Jan 1, 1980·International Journal of Gynaecology and Obstetrics : the Official Organ of the International Federation of Gynaecology and Obstetrics·A V SchallyA Arimura
May 21, 2014·Nature Reviews. Clinical Oncology·Yien Ning Sophia WongJohann de Bono
Jun 5, 2002·Nature Reviews. Cancer·Samuel R Denmeade, John T Isaacs
Jan 27, 2004·The Prostate·Samuel R Denmeade, John T Isaacs
Jan 1, 1984·Medical Oncology and Tumor Pharmacotherapy·A V SchallyA M Comaru-Schally

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