Effect of inhibin on rat testicular desoxyribonucleic acid (DNA) synthesis in vivo and in vitro

Abstract

Abstract. When injected in vivo 3 h before sacrifice or when incubated in vitro with testicular fragments for 3 h, tritiated thymidine, a reliable index of DNA synthesis and of mitotic activity, was incorporated into the DNA of differentiated spermatogonia, as shown by autohistoradiography. The maximum DNA specific activity was obtained in pubertal rats aged 42 days, weight 150 g. Two preparations of inhibin extracted from ram rete testis fluid (RTF) of different molecular weight (> 10 000 for RTF1 and < 5000 for RTF3) but which possess the same biological properties were investigated for their effect on thymidine uptake in vivo and in vitro. In vivo both preparations specifically inhibited tritiated thymidine incorporation into testicular DNA of pubertal animals (42 days). No change in thymidine uptake into hepatic DNA was observed. Tritiated thymidine incorporation into testicular DNA was lower in normal adult rats and in hypophysectomized pubertal animals. RTF1 and RTF3 did not affect thymidine incorporation in either case. The reasons for this lack of effect are discussed. In vitro, both preparations induced a dose-dependent decrease in DNA synthesis in testis fragments from rats aged 42 and 49 days. The preparations lost their in vivo and in vitro inhibitory effects when denatured by heating and trypsin digestion. The inhibin preparations probably reduced testicular DNA synthesis and spermatogonial multiplication by reducing FSH secretion in vivo but also had a direct effect on the germ cells as shown by the in vitro experiments. These in vivo and in vitro actions of inhibin preparations are similar to those of the testicular chalones. The relationship which might exist between inhibin and the chalones is discussed.

Expression and Cellular Localization of Inhibin .ALPHA.-Subunit mRNA in Equine Fetal Gonads.

“…In addition, inhibin stimulated androgen secretion from theca-interstitial cells of the rat [10] and human [8] in vitro, and inhibin also enhanced LH/hCG-induced androgen synthesis when added to a newborn rat Leydig cell culture [10], while activin suppressed it [10]. These reports suggest that in both the equine fetal ovary and testis, inhibin produced from interstitial cells might play a paracrine/autocrine role in the regulation of androgen production, and inhibin produced from Sertoli cells might be suppressing spermatogonial development as reported in the rat [4,22]. Further studies to elucidate the precise roles of inhibin and/or inhibin α-subunit related molecules in equine fetal gonads are awaited.…”

“…This does not, however, exclude the possibility that inhibin and/or inhibin α-subunit related molecules probably produced in equine fetal gonads might be functioning as paracrine/autocrine factors. The functions of inhibin within gonads has been shown by some investigators: inhibin produced from Sertoli cells during the spermatogonial development in the rat was reported to be acting as an inhibitory paracrine factor [4,22], while activin stimulated spermatogonial proliferation [11]. In addition, inhibin stimulated androgen secretion from theca-interstitial cells of the rat [10] and human [8] in vitro, and inhibin also enhanced LH/hCG-induced androgen synthesis when added to a newborn rat Leydig cell culture [10], while activin suppressed it [10].…”

“…and inhibition of spermatogenesis in adult rat testes [4,22]. The expression of inhibin α-subunit mRNA and its protein was also found in fetal gonadal tissues of the rat [18,19], humans [3,16] and rhesus monkeys [16], and its role during gonadal development has been predicted [3,16,18,19].…”

Expression of Inhibin a-Subunit in Horse Testis.

“…Recently, however, it was reported that inhibin was an endocrine hormone functioning primarily on reproductive tissues in paracrine and autocrine fashions [5,15,19]. In the testis, inhibin appeared to decrease spermatogonial mitotic activity [9,30] and to regulate Leydig cell function [11,15]. It also enhanced LH-mediated androgen production in Leydig cells [11,15].…”

Rôle des facteurs de croissance et cytokines dans le testicule normal et pathologique

“…Ces facteurs pourraient contr61er la survie (SCF, [38]), la m u l t i p l i c a t i o n des s p e r m a t o g o n i e s (EGF/TGFa, bFGF, IGF I ; [23,30,61,64,73]), l'arr6t de la multiplication de ces cellules (TGFb, [18] ; inhibine, [16,81] de signalisation vis-a-vis des hormones (FSH, testosterone) ( Figure 3). Cependant, rexpression de ces facteurs sertoliens peut ~tre aussi sous le contrSle de facteurs locaux comme le TNFa, l'ILla ou le NGF, provenant des cellules germinales.…”