NONCOORDINATED EXPRESSION OF LUTEAL CELL MESSENGER RIBONUCLEIC-ACIDS DURING HUMAN CHORIONIC-GONADOTROPIN STIMULATION OF THE PRIMATE CORPUS-LUTEUM

In nonfertile cycles, the absolute steroidogenic capacity of the prima te corpus luteum, as reflected in the expression of messenger RNA (mRN A) for the progesterone biosynthetic enzymes cytochrome P450 cholester ol side-chain cleavage (P450SCC) and 3beta-hydroxysteroid dehydrogenas e (3beta-HSD), progressively declines until luteal regression. Despite this progressive loss in luteal cell function, the elaboration of CG by the implanted blastocyst is able to prolong the functional lifespan of the corpus luteum. It was the purpose of this study to investigate the relationship between aging of the primate corpus luteum and the c ellular mechanisms by which the decline in luteal cell function is arr ested by CG. Corpora lutea were obtained from cynomolgus monkeys on da ys 11 or 16 of the luteal phase after a 7-day treatment period with in creasing doses of human CG (hCG) given intramuscularly beginning on da ys 5 or 10. Corpora lutea were also obtained from control animals on d ays 5, 10, 11, and 16 of the luteal phase. Human CG treatment signific antly (P < 0.05) elevated both serum progesterone and estradiol levels throughout the treatment period; however, progesterone production in animals treated with hCG late in the luteal phase (days 10-16) steadil y declined after the third treatment day. Expression of mRNA for P450s cc and 3beta-HSD was markedly stimulated (P < 0.05) by hCG treatment e arly in the luteal phase. However, 3beta-HSD message levels in corpora lutea from animals treated with hCG on days 10-16 were not different from those of day-16 control corpora lutea, whereas P450scc mRNA was o nly minimally stimulated. There was a dramatic (P < 0.05) increase in mRNA levels for the aromatase enzyme and low density lipoprotein recep tor in animals given hCG in both the early and the late luteal phase. In conclusion, there appears to be a differential responsiveness of th e primate corpus luteum to hCG stimulation dependent upon luteal age. The loss in responsiveness to hCG in terms of maintenance of mRNA leve ls is reflective of the inability of the late luteal phase corpus lute um for continued progesterone biosynthesis in the face of heightened l uteotropic stimulation.