Delay of puberty and inhibition of reproductive processes in the rat by a gonadotropin-releasing hormone agonist analog.

Studies were performed in immature and mature female rats to determine the effects of chronic administration of [D-Leu6,des-Gly-NH210, Pro-ethylamide9]-gonadotropin-releasing hormone (GnRH) upon maturation and maintenance of reproductive function. Treatment of immature rats inhibited normal overian growth and maturation as evidenced by arrest of uterine growth, delay of vaginal opening, and absence of normal cycling. The primary responses in the mature animal were cessation of cycling, atrophy of the ovaries to a "prepuberal" size, and uterine weight regression. In both groups termination of treatment was followed by prompt restoration of normal ovarian mass and function, including support of breeding processes. The results presented here suggest that chronic administration of the GnRH analog inhibits ovarian steroid output either by direct action of the analog on the ovary or indirectly through qualitative or quantitative changes in levels of luteinizing hormone and follicle-stimulating hormone.