Abstract.
Cultures of rat anterior pituitary cells were utilized to examine the role of 5α reduction in the inhibitory action of testosterone on LRH-induced LH release. Cultures were pre-treated with steroids for 48 h and then incubated 6 h with steroids plus 5 × 10−10 m LRH, the approximate EC50 for LH and FSH release. Testosterone inhibited LRH-induced LH release with an IC50 of approximately 2 × 10−10 m. However, even relatively high concentrations of testosterone did not completely inhibit LRH-induced release. Testosterone (and dihydrotestosterone) appeared to antagonize LRH-induced LH release but did not markedly affect 48 h basal release or LH synthesis as judged by the quantity of LH released plus that remaining intracellularly. Progesterone (10−6 M) and heparin (1000 U/ml) were used as inhibitors of anterior pituitary steroid 5α reductase. Progesterone, when combined with testosterone, markedly shifted the testosterone inhibition curve to the right (approximately 340-fold) but did not shift the dihydrotestosterone inhibition curve. Heparin also slightly shifted the testosterone inhibition curve (approximately 2.4-fold) to the right. These observations support the hypothesis that the mechanism of action of testosterone on the anterior pituitary involves 5α reduction.