EFFECTS OF LUTEINIZING-HORMONE (LH) AND ANDROGEN ON STEADY-STATE LEVELS OF MESSENGER-RIBONUCLEIC-ACID FOR LH RECEPTORS, ANDROGEN RECEPTORS,AND STEROIDOGENIC ENZYMES IN RAT LEYDIG-CELL PROGENITORS IN-VIVO

Adult Leydig cells differentiate postnatally from mesenchymal-like pro genitor cells. The relative scarcity of LH receptors (LHRs) in progeni tor cells indicates that additional hormones may be important in the i nitial phases of Leydig cell differentiation. High levels of androgen receptor (AR) in progenitor cells point to a role for androgen in thes e cells. In the present study, an LHRH antagonist, 2Nal(1),4C1DPhe(2), D3Pal(3),Arg(5),DGlu(6)(anisole adduct), DAla(10)]GnRH (NalGlu; 250 mu g/kg body weight), was used to suppress endogenous secretion of both LH and androgen during days 14 to 21 postpartum in vivo. To examine th e effects of LH and androgen on regulation of Leydig cell progenitors (PLCs), exogenous LH (5 mu g/day), testosterone (T; 30 mu g/day), or b oth were administered to NalGlu-treated rats. After 7 days of treatmen t, we examined the effects on testis weight, Leydig cell morphology, a nd T production. The steady state messenger RNA (mRNA) levels for LHR, AR, cytochrome P450 17 alpha-hydroxylase, and 3 alpha-hydroxysteroid dehydrogenase in purified PLCs were measured by reverse transcription- polymerase chain action, with ribosomal protein S16 as the internal co ntrol. Treatment with NalGlu significantly decreased testis weight, re sulted in an abundance of mesenchymal-like cells over immature Leydig cells, lowered T production, and reduced the levels of several Leydig cell mRNAs. Treatment with exogenous LH or T maintained testis weight and Leydig cell morphology in NalGlu-treated rats. The mRNA levels for LHR, AR, and 3 alpha-hydroxysteroid dehydrogenase were significantly increased by LH or T. P450 17 alpha-hydroxylase mRNA levels were eleva ted by LH to control level but strikingly reduced by T. Combined treat ment with LH and T further increased basal T production but did not el evate mRNAs beyond the levels obtained with each hormone alone. LH and androgen act similarly in PLCs in promoting Leydig cell differentiati on with respect to morphological and molecular landmarks. These findin gs support the hypothesis that androgen as well as LH is involved in t he differentiation of immature Leydig cells from mesenchymal-like prog enitors.