Development of δ 5,3β-Hydroxysteroid and Glucose-6-Phosphate Dehydrogenase in the Testes,Adrenals and Ovaries of the Rabbit Fetus 1

Abstract

The classical work of Jost demonstrating the fetal testicular control of masculine differentiation was performed in the rabbit (1). Orchiectomy produced testosterone-reversible blockade of androgen-dependent masculine development between days 19 and 22 of gestation but had no effect after day 22. Decapitation, performed on male fetuses before day 22, resulted in a gonadotropin-reversible partial block in masculine differentiation manifested by hypospadias, suggesting that hypophysectomy induced deficient testicular function. The fetal ovary did not play a role in sexual differentiation of the rabbit fetus. Jost has also shown that there is a pituitary-dependent early period of growth of the rabbit fetal adrenal cortex between days 20 and 25 (2). From day 25 to day 28 he has demonstrated a cortisone- and ACTH-dependent increase in fetal liver glycogen, which does not occur in adrenalectomized or decapitated fetuses in pregnant rats whose corticosteroid production is eliminated by adrenalectomy.

Conversion of δ⁵, 3β-hydroxysteroids to the corresponding δ⁴, 3-ketones is necessary for biosynthesis of virtually all biologically active steroid hormones (3). These reactions are catalyzed by two steroidogenic enzymes, 3β-hydroxysteroid dehydrogenase and δ^5-4, 3-ketosteroid isomerase. Activity of glucose-6-phosphate dehydrogenase provides NAD PH which is the coenzyme required for steroid hydroxylations and cleavage of cholesterol and C_17-20 side-chains. Although previous sequential histochemical analyses of these enzymes in the adrenals and testes of the human (4) and rat fetus (5) have suggested a temporal correspondence of enzymatic activity to embryonic function or dysfunction of these tissues, the semiquantitation of the histochemical method has been questioned (6). Moreover, the validity of the observation that development of these ovarian enzymes begins prenatally in the human but postnatally in the rat has been challenged because of the use of human postmortem tissue (6).

In this report we have studied the development of these enzymes in the fetal testes, adrenals and ovaries of the rabbit with the semiquantitative histochemical technique and with a quantitative method sensitive enough to detect the low level of activity of the dehydrogenase system in individual rabbit fetal tissues.