Adult male transgenic mice expressing the human growth hormone (hGH) gene are hypoprolactinemic. To evaluate the effects of exogenous prolactin (PRL) and endogenously secreted hGH on pituitary and Leydig cell function, adult male transgenic and nontransgenic mice (10-16 wk of age) were treated s.c. with either saline-polyvinylpyrrolidone (PVP) or oPRL (100 micrograms/mouse) in saline-PVP. Animals were treated twice daily; a total of 7 injections were given. One hour after the last injection, each group of mice was treated i.p. either with saline or oLH (0.3 microgram/g BW); 2 h later, blood was obtained via heart puncture. Plasma FSH, LH, PRL, androstenedione (A-dione), and testosterone (T) levels were measured by validated RIAs. Basal PRL levels were significantly lower (p less than 0.001) and basal LH concentrations were significantly higher (p less than 0.01) in transgenic than in nontransgenic mice. Administration of PRL significantly decreased (p less than 0.01) plasma LH levels in transgenic mice, whereas similar treatment of nontransgenic mice increased (p less than 0.01) circulating LH concentrations. Plasma FSH levels were unaffected in transgenic and nontransgenic mice treated with saline or PRL. Basal plasma A-dione and T levels were similar in both groups of animals and were significantly increased after treatment with LH. Administration of PRL increased T levels in transgenic and nontransgenic mice, but the T response to LH treatment was greater in PRL-treated transgenic mice, indicating the synergistic effect of hGH in the biosynthesis of T.(ABSTRACT TRUNCATED AT 250 WORDS)