Effect of LH injections on testicular steroidogenesis, cholesterol side-chain cleavage P450 mRNA content and Leydig cell morphology in hypogonadal mice

Abstract

Hypogonadal (hpg) mice have a congenital deficiency of hypothalamic gonadotrophin-releasing hormone (GnRH) and the gonads consequently lack exposure to gonadotrophins during development. We injected male hpg mice with LH for 10 days to investigate whether LH alone can stimulate normal steroidogenesis in these animals. Control animals had an inactive interstitium and very few germ cells. Testicular content of androgens was undetectable by radioimmunoassay in control animals unless a single injection of LH was given 1 h before death, when androgens were just detectable. Control testes incubated in vitro with [3H]pregnenolone demonstrated that without gonadotrophin stimulation pregnenolone was metabolized only to progesterone in significant amounts. Assay for cholesterol side-chain cleavage cytochrome P450 (P450scc) mRNA showed basal expression in saline-treated hpg mouse testis. LH treatment induced hypertrophy and hyperplasia of Leydig cells and division of germ cells. Testicular androgen content increased significantly, with testosterone and androstenedione as the major androgens. LH-treated testes incubated with [3H]pregnenolone in vitro had a greater synthetic capacity for testosterone, suggesting an increase in 17 alpha-hydroxylase/C17-20-lyase activity. Basal and human chorionic gonadotrophin-stimulated androgen production in vitro increased markedly following LH treatment to levels previously described in the normal adult animal. LH treatment caused a rapid and transient increase in the hybridization of P450scc mRNA which was sevenfold greater than that of saline-treated controls when the animals were killed 1 h after the last injection but fell to control levels within 24 h of cessation of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Direct Exposure of Guinea Pig CNS to Human Luteinizing Hormone Increases Cerebrospinal Fluid and Cerebral Beta Amyloid Levels

“…In gonadal tissues, P450scc converts cholesterol to the steroid precursor, pregnenolone, and it is up-regulated when the LHR signalling pathway is activated in vivo[35] and in vitro [36,37]. Components of the LHR signalling pathway have been shown to be present in neuronal cells [5,13,14,15,17] and in rodent brain [29].…”

Effects of ACTH and expression of the melanocortin-2 receptor in the neonatal mouse testis

“…Thus, increased expression of Star mRNA in neonatal mouse testis by hCG and ACTH is consistent with both hormones acting through similar signaling pathways in mouse fetal Leydig cells. It is known that LH acts to regulate and maintain expression of Cyp11a1 in the testis (Malaska & Payne 1984, Mason et al 1984, Scott et al 1990) and studies using MA-10 cells have shown that the effects of LH can be rapid (Mellon & Vaisse 1989). The effects of LH and ACTH on Cyp11a1 in the isolated testicular cells reported here are consistent, therefore, with these earlier studies.…”

The expression level of frog relaxin mRNA (fRLX), in the testis of Rana esculenta, is influenced by testosterone

“…In mammals, other studies reported that LH/hCG is essential to induce relaxin-like factor (RLF) expression in the adult Leydig cells of the mouse (Balvers et al, 1998). However, a pituitary control of RLF has been indicated, using hypogonadic mice lacking an active pituitary-gonadal axis caused by a deletion in the hypothalamically expressed gene for GnRH, with consequent gonadotropin deficiency (Scott et al, 1990;Cattenach et al, 1997;Charlton et al, 1983). Here, RLF expression is totally absent, suggesting that Leydig cells seem to be arrested in a prepubertal state of differentiation (Balvers et al, 1998).…”