Direct effects of propylthiouracil on testosterone secretion in rat testicular interstitial cells

Abstract

1 The aim of this study was to investigate the mechanism by which propylthiouracil (PTU) exerts its inhibitory e ects on the production of testosterone by rat testicular interstitial cells. 2 The plasma testosterone concentration was decreased 60 and 120 min after an intravenous infusion of PTU (10 or 20 mg kg 71 ), but the concentration of plasma T 4 was una ected by the drug treatment.3 Exposure of anterior pituitary tissue to PTU (3 ± 12 mM) in vitro did not a ect either basal or gonadotropin-releasing hormone (GnRH)-stimulated luteinizing hormone (LH) release. 4 PTU (3 ± 12 mM) inhibited both the basal and the human chorionic gonadotropin (hCG, 0.05 iu ml 71 )-stimulated release of testosterone from rat testicular tissue in vitro; at the highest concentration tested (12 mM), it also inhibited the forskolin or 8-bromo-adenosine 3':5'-cyclic monophosphate (8-Br-cyclic AMP)-stimulated release of testosterone. 5 The 25-OH-cholesterol (10 77 ± 10 75 M)-stimulated release of pregnenolone and testosterone by the testicular interstitial cells was inhibited by PTU (12 mM, P50.05). 6 The results suggest that the inhibitory actions of PTU on testosterone secretion are exerted, at least in part, at the testicular level through a mechanism which is independent of thyroid status and which involves a reduction in P450scc activity and, hence, in the conversion of cholesterol to pregnenolone.

Inhibition of Testosterone Production by Propylthiouracil in Rat Leydig Cells1

“…The dosages of drugs are expressed in their final molar concentrations in the flask. The dosages of PTU used in this study were the same as those we used in a previous study [14]. Dosages were higher than the clinical dose (200-600 mg per person per day) [15,16] but in the range of that used previously in rodent studies [17].…”

“…Testicular interstitial cells were isolated with the collagenase dispersion method as previously described [14]. The procedure used for preparing Leydig cells has been described elsewhere [18].…”

“…The concentrations of pregnenolone were determined by radioimmunoassay as described previously [14]. The sensitivity of the pregnenolone radioimmunoassay was 16 pg per assay tube.…”

“…PTU decreased both the adrenocortical response to ACTH in vivo and corticosterone production by rat zona fasciculata-reticularis cells [13]. PTU also decreases the production of testosterone in rat testicular interstitial cells [14]. These thyroid hormone-independent results indicate that PTU acts directly on the steroidogenic organs.…”

Effects of Propylthiouracil on Testicular Tissue in Undescended Testes of Newborn Rats

“…PTU is an anti-thyroid drug which inhibits both the synthesis of thyroid hormones in the thyroid gland and the conversion of T 4 to its active form T 3 in peripheral tissues [7] . In previous studies it has been emphasized that the adult testes were unresponsive to thyroid hormones but currently the important role of T 3 on the function of the testes is stressed [5] .…”