Ovulation Induced by Synthetic Luteinizing Hormone Releasing Factor in Androgen-Sterilized Female Rats

Abstract

It is well known that administration of a single injection of testosterone propionate to newborn female rats results in permanent anovulatory sterility. After puberty these animals show permanent vaginal cornification and their ovaries contain follicles but no corpora lutea (Barraclough, 1961). One of the most important lesions in these rats seems to be a blockade of the pre-ovulatory discharge of luteinizing hormone releasing factor (LH-RF) from the median eminence.Porcine LH-RF has been shown to be a decapeptide, pyro Glu-His-Trp-Ser-Tyr\x=req-\ Gly-Leu-Arg-Pro-Gly(NH2), and when this polypeptide was synthesized it was found to have follicle-stimulating hormone releasing factor activity as well (Matsuo, Matsuo, Baba, Nair, Arimura & Schally, 1971). In the present experiments we posed the question of whether a subcutaneous injection of synthetic LH-RF could induce ovulation in androgen-sterilized female rats, and if so, whether this would be a dose-dependent effect.Albino rats of the Sprague\p=m-\Dawley strain kept in light-controlled quarters were used. On the morning of the 3rd day after birth female rats were given 10, 50, 100 or 1000/¿g testosterone propionate, subcutaneously. Two weeks before autopsy vaginal smears were taken and only rats showing persistent cornification of the vaginal mucosa were used. The LH-RF decapeptide was synthesized in our laboratory by a conventional fragment condensation method. Its homogeneity was examined by thin-layer chromatography and electrophoresis. The amino acid composition, amino acid sequence and optical rotation ([a]ff = -49°, in 1 % acetic acid) of the

Identification of genes involved in the onset of female puberty of rat

“…Puberty was clearly delayed and the gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) surges disappeared by destruction of hypothalamo-pituitary-gonadal axis (Hayashi and Aihara, 1989;1993;Pinilla et al, 1993). The sterility observed in the ESR was reported to be due to the lack of neural circuits regulating the release of GnRH (Borvendeg et at., 1972;Mennin et al, 1974;Hayashi et al, 1991). Together with these results, neonatal treatment of estrogen may cause changes in the organizational pattern of the brain areas responsible for the sexual differentiation and behaviors preceding the normal pubertal process.…”

Studies on the structure—activity relationships of synthetic LHRH analogs

“…The ovulation inducing activities of LHRH analogs have been studied in diestrus rats employing the method of Yamasaki and Nakayama [6] and in androgen sterilized female rats by a procedure developed in our laboratory [7].…”

Ovulation Induced by LH-RH in Rats Made Anovulatory by Various Experimental Procedures

“…The pituitary responsiveness of NA500 animals did not seem to differ from that of the controls, for the slightly higher amount of LH-RH required for full ovulation in NA500 animals, as compared with control values, was probably necessary for the release of an amount of LH adequate to overcome the ovarian insensitivity which follows androgenization. Ovaries from NA500 rats in fact require approximately 5-10 times as much exoge nous LH as ovaries from normal females, before they show an equivalent ovulatory response [Segal and Johnson, 1959;Astrada et al, 1969; U ilenbrook and Van der Werff ten Bosch, 1972; Mennin et al, 1974], Previously, it was demonstrated that the pituitaries of androgenized female rats are capable of releasing an ovulatory quota of LH in response to sheep hypothalamic extract [Johnson, 1963] and to synthetic LH-RH [Borvendég et al, 1972]. The present work shows that the pituitary glands of normal and androgenized rats are equivalent in their sensitivity to LH-RH, as reported by Mennin et al [1974], Furthermore, the comparable responsiveness to LH-RH is an indication that androgenized females' pituitaries respond as if they were under hormonal conditions comparable to those of a preovulatory proestrous female.…”