Influence of thyroid hormone on androgen metabolism in peripuberal rat Sertoli cells

Abstract

Abstract The aim of the present study was to investigate the influence of thyroid hormones on androgen metabolism in Sertoli cells isolated from 3- and 4- week-old rats. Hypothyroidism was induced by the oral administration of 0·025% methimazole (MMI) from birth until the rats were killed at 3 and 4 weeks of age. Half of the MMI-treated animals were injected i.p. with l-tri-iodothyronine (T3 3 μg/100 g body weight) during the last week before death. Sertoli cells from all groups were initially cultured under basal conditions for the first 24 h and subsequently in the presence of testosterone with or without T3 for an additional 24 h. Hypothyroidism was associated with severe impairment of body as well as testicular growth. Indeed, body and testicular weights were similar in 4-week-old hypothyroid animals to those in 3-week-old control rats. Testosterone metabolism in Sertoli cells isolated from 3- and 4-week-old hypothyroid rats was mainly expressed by the lowering of 5α-dihydrotestosterone + androstane 3α, 17β–diol and an enhanced formation of 5α-reduced steroids with poor androgenic properties (e.g. 5α–androstane, 3, 17α-dione (androstanedione), 5α–androstan, 3-ol-17-one (androsterone)). Treatment of the same group of animals with T3 in vivo and in vitro did not influence the pattern of 5α–reductase steroids substantially. The most striking finding in the Sertoli cells of 3-week-old hypothyroid rats was the dramatic enhancement of oestradiol formation which persisted to a lesser extent 1 week later. Oestradiol formation was greatly decreased by the addition of T3 in vivo and in vitro in hypothyroid animals. These results suggest that T3 might influence androgen metabolism during the functional maturation of Sertoli cells. Journal of Endocrinology (1994) 140, 349–355