Role of testosterone in the induction of hepatic peroxisome proliferation by clofibrate.

Hepatic peroxisome proliferation is induced by a number of agents, including clofibrate. Sustained proliferation of peroxisomes is associated with the development of hepatocellular carcinoma. In the present study, we have investigated the role of testosterone in peroxisome proliferation induced by clofibrate. Three groups of male rats (intact, castrated, and castrated replaced with testosterone) were studied. Proliferation of peroxisomes was induced by feeding clofibrate (0.25%, 0.50%, and 1.0% of diet) for 2 weeks. Peroxisome proliferation was monitored by measuring total peroxisomal beta-oxidation activity. In intact rats, the peroxisomal beta-oxidation activity (nmol/min/mg protein) increased in a dose-dependent manner and was 7.2 +/- 0.4, 52.6 +/- 7.5, 63.2 +/- 3.7, and 92.4 +/- 4.0 at clofibrate doses of 0%, 0.25%, 0.50%, and 1.0%, respectively. In contrast, in castrated rats, the total peroxisomal beta-oxidation activity was significantly (P < .01) lower at clofibrate levels of 0.25% and 0.50% (25.8 +/- 2.7 and 42.5 +/- 2.2, respectively), but not at the clofibrate level of 1.0% (85.0 +/- 6.3). Testosterone replacement of castrated rats restored the peroxisomal beta-oxidation activity. To determine whether the above results were related to the metabolism of clofibrate in the absence or presence of testosterone, we measured serum clofibrate levels. These levels were 50% lower in castrated rats than in intact rats or in testosterone-treated castrated rats. The activity of hepatic uridine diphosphate (UDP)-glucuronyltransferase, the enzyme catalyzing the glucuronidation of clofibrate, was measured using either bilirubin or 4-methylumbelliferone as substrates and was found to be unaffected by castration or testosterone treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

The follicle stimulating hormone-inhibin feedback loop in male primates.

This paper reviews our current knowledge of the role of testicular inhibin in the regulation of follicle stimulating hormone (FSH) secretion in the rhesus monkey. Species differences between monkey and rat are described, and evidence for and against the hypothesis that control of FSH secretion in the human male is similar to that for the monkey is presented.

Inhibin is released together with testosterone by the human testis.

The secretion of inhibin by the testis into the circulation was studied by measuring immunoreactive inhibin concentrations in spermatic vein blood samples drawn at 15 min intervals for 4 h. Mean spermatic vein inhibin levels were four times the levels in peripheral blood whereas spermatic vein testosterone (T) levels were 60-fold increased. Inhibin was released in well-defined pulses which coincided with episodes ot T release; both the duration and relative amplitude of inhibin and T pulses were similar. Inhibin pulses were undetectable in peripheral blood. These data suggest that the mechanism responsible for releasing T from the testis also stimulates inhibin release. This mechanism appears to involve LH and Leydig cells.

The effect of oxytocin administration upon the pulsatile secretion of luteinizing hormone in humans.

The effect of iv administration of synthetic oxytocin upon the pulsatile pattern of LH secretion was studied in 5 healthy men and 10 healthy women. Five of the women were studied in the follicular phase of a menstrual cycle and the other 5 were studied in the luteal phase of a cycle. Synthetic oxytocin in 0.9% saline or saline alone was administered via continuous iv infusion for 8 h on 2 consecutive days. Infusions were administered using a double-blinded and radomized schedule. The rate of the oxytocin infusion commenced at 1 mU min and was increased 1 mU/min every 40 min to a final rate of 12 mU min. The plasma oxytocin concentration during oxytocin infusion ranged from 2-70 fmol 1. Blood for LH determination was sampled every 20 min in the 5 follicular phase women and every 10 min in the 5 men and 5 luteal phase women. The detect algorithm was used to analyze LH pulsatile secretion. Oxytocin infusion was without significant effect on mean LH, number of LH pulses, or area under the LH curve in men or women studied for the period of observation. Thus it is unlikely that increases in plasma oxytocin regulate the pulsatile secretion of LH in humans.