Biosynthesis of steroid hormones in human endocrine tissue and in the rat testis

Henry Crawford Ford
This thesis reports the results of studies on steroid metabolism in a subject with an adrenocortical carcinoma and hypoglycemia, in the testes obtained from a subject with virilizing male pseudohermaphroditism and in the testes of the normal rat. Incubations of cell-free homogenates of an adrenocortical carcinoma from a 51 year old female with severe hypoglycemia were performed using ³H-pregnenolone and ¹⁴C-progesterone as substrates. Transformation of ³H-pregnenolone to progesterone,
more » ... esterone, dehydroepiandrosterone and androstenedione was observed; no metabolites of ¹⁴C-progesterone were detected. The excretion rate in urine of 3α ,17,21-trihydroxy-5β -pregnan-20-one, a metabolite of cortexolone, was elevated which suggests that a defect in 11β -hydroxylase activity was present. The excretion rates in urine of total 17-ketosteroids, 17-hydroxycorticoids and 17-ketogenic steroids were elevated; the excretion rates of testosterone, dehydroepiandrosterone, pregnandiol, pregnanetriol and free cortisol were not elevated. The etiology of the hypoglycemia that may accompany some adrenocortical tumors remains unknown. It was not possible to relate the results of the investigations of steroid metabolism reported herein to the hypoglycemia that was present. Steroid biosynthesis in vitro was investigated in testes obtained during puberty from a 14 year old subject with virilizing male pseudohermaphroditism. Cell-free homogenates of gonadal tissue efficiently metabolized ³H-pregnenolone, ¹⁴C-progesterone and ¹⁴C-androstenedione to testosterone; formation of estrone and estradiol-17β was not detected. 16α-Htdroxyprogesterone was formed from both ³H-pregnenolone and ¹⁴C-progesterone. The results are similar to those of others who have investigated the steroidogenic capacity of gonadal tissue in patients with male pseudohermaphroditism and feminization at puberty. A defect in the formation of progesterone from pregnenolone has been suggested to explain the results of a previous study in which the gonadal tissue obtained from a pa [...]
doi:10.14288/1.0102216 fatcat:2ybgqy3cwrhdblj4igyoh2z5h4