Germ cell-specific cyclic adenosine 3 ',5 '-monophosphate response elementmodulator expression in rodent and primate testis is maintained despite gonadotropin deficiency

cAMP response element modulator (CREM) is an important component of the cAM P-mediated signaling pathway and is essential for differentiation of haploi d male germ cells. in the rodent, testicular expression of CREM is believed to be controlled by FSH. We studied the expression pattern of CREM and gon adotropic control in the nonhuman primate and rodent testis. Adult cynomolg us monkeys (Macaca fascicularis) received daily either vehicle or the poten t GnRH antagonist (ANT) cetrorelix for periods of 25 and 56 days. Rats were also exposed to vehicle or ANT for periods of 14 and 42 days. ANT treatmen t suppressed pituitary gonadotropin secretion, reduced testis size, and alt ered spermatogenesis. A rabbit polyclonal antibody raised against recombina nt CREM, and reacting with CREM alpha, -beta, -gamma, -tau 1 and -tau 2 at similar affinities was used for immunocytochemistry and Western blotting. C REM expression was seen in round spermatids, with highest levels during spe rmatogenic stages V-VII, but declined with progression of spermatid develop ment in the primate. Similar observations were made for the rat testis. Thu s, CREM expression was maximal at the onset of acrosome formation and was l ow or undetectable upon initiation of spermatid elongation in both species. A weak, but specific, CREM signal was seen in mid- to late pachytene sperm atocytes and during meiotic division in both species. After ANT exposure, t he germ cell- and stage-specific pattern of CREM expression was quantitativ ely retained at all time points and in both species. Northern and Western b lot analysis confirmed the maintenance of testicular CREM expression despit e 25 days of ANT treatment. A retrospective immunocytochemical analysis of rat testes 14 days posthypophysectomy revealed CREM signals in round sperma tids. These findings demonstrate that the testicular expression of CREM is not entirely dependent on gonadotropic hormones but, rather, on the maturat ional stage of haploid round germ cells.