Paradoxical effects of D-Trp6-luteinizing hormone-releasing hormone on the hypothalamic-pituitary-gonadal axis in immature female rats.
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.
D000715:Anatomy; D000818:Animals; D001835:Body Weight; D004958:Estradiol / Q000097:blood; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D006062:Gonadotropins / Q000097:blood; D006065:Gonadotropins, Pituitary; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D010053:Ovary / Q000033:anatomy & histology; D010902:Pituitary Gland; D011374:Progesterone / Q000097:blood; D051381:Rats; D012741:Sexual Maturation; D014599:Uterus / Q000033:anatomy & histology
D006062:Gonadotropins; D006065:Gonadotropins, Pituitary; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D004958:Estradiol