Work

Direct inhibition of rat testicular androgen biosynthesis by arginine vasotocin. Studies on mechanisms of action.

Year: 1982

Type: article

Abstract: The mechanisms of the direct antigonadal action of arginine vasotocin (AVT) were investigated in vitro in a primary culture of testis cells from adult hypophysectomized rats.Treatment with AVT did not affect testosterone production, while treatment with human chorionic gonadotropin (hCG) led to 30-80-fold increases in testosterone production.In contrast, concomitant treatment with increasing concentrations of AVT led to a dose-dependent inhibition of the hCG-stimulated accumulation of testosterone (median effective dose = 6.3 & 0.3 X 10"' M).This inhibitory effect of AVT was partially reversible upon removal of the hormone.Arginine vasopressin and lysine vasopressin also inhibited hCG-stimulated androgen biosynthesis but 16 other peptides were without effect.Treatment with AVT did not interfere with the binding of hCG to its receptors and was not associated with alterations in the total cell number, cell viability, cellular DNA, or protein content.In contrast, AVT inhibited N6,02"dibutyryl adenosine 3':5'-cyclic monophosphate-stimulated accumulation of testosterone, suggesting that AVT may act a t steps distal to CAMP formation.Measurement of the steroid precursors of testosterone indicated that concomitant treatment with AVT inhibited the hCG-stimulated accumulation of 17a-hydroxyprogesterone (67% reduction) and androstenedione (87% reduction) but increased pregnenolone (3.5-fold) and progesterone (9.6-fold) production.Provision of exogenous progesterone or 17a-hydroxyprogesterone increased androgen production but failed to overcome the AVT-induced inhibition of the accumulation of testosterone and androstenedione.Thus, the inhibitory effect of AVT on testicular androgen biosynthesis is due, at least in part, to selective suppression of the enzymes 17a-hydroxylase and 17-20 desmolase.Arginine vasotocin, the most primitive neurohypophysial hormone of the vertebrates (1, 2) and one that has been

Source: Journal of Biological Chemistry

DOI: 10.1016/s0021-9258(19)68191-3

Authors: E.Y. Adashi, A.J. Hsueh

Institutions: University of Maryland, Baltimore, University of California San Diego

Language: English

Topic: Hypothalamic control of reproductive hormones

Subfield: Reproductive Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,430