DIFFERENTIAL REGULATION OF STEROIDOGENIC ENZYMES DURING DIFFERENTIATION OPTIMIZES TESTOSTERONE PRODUCTION BY ADULT-RAT LEYDIG-CELLS

The postnatal differentiation of rat Leydig cells may be subdivided in to three steps based on morphology and steroid production. The purpose of this study was to clarify the developmental mechanisms underlying increased testosterone production by measuring steady state levels of the mRNAs for three steroidogenic enzymes in isolated Leydig cells at each stage of differentiation. These include Leydig cell progenitors o n day 21, immature Leydig cells on day 35, and adult Leydig cells on d ay 90. The steroidogenic enzymes were 1) cholesterol side-chain cleava ge enzyme (CSCC), 2) 17alpha-hydroxylase (P450-17alpha), and 3) 3alpha -hydroxysteroid dehydrogenase (3alphaHSD). We report that levels of CS CC and P450-17alpha mRNAs increase, whereas 3alphaHSD mRNA levels decl ine during the course of Leydig cell differentiation. The levels of 3a lphaHSD mRNA were high in progenitor Leydig cells that appeared to con tain little smooth endoplasmic reticulum and decreased in cells as smo oth endoplasmic reticulum developed and other enzyme mRNAs increased. These observations suggest that the factors that regulate 3alphaHSD mR NA levels are startlingly different from those that regulate the mRNA levels of CSCC and P450-17alpha. We conclude that the progressive incr ease in the capacity of differentiating Leydig cells to produce testos terone can be explained in part by an increase in the activity of enzy mes that synthesize testosterone (CSCC and P450-17alpha) and a decreas e in the activity of an enzyme that metabolizes testosterone and its p recursors (3alphaHSD).