Role of luteinizing hormone in the expression of cholesterol side-chain cleavage cytochrome P450 and 3 beta-hydroxysteroid dehydrogenase, delta 5-4 isomerase messenger ribonucleic acids in the primate corpus luteum.

Abstract

It is well established that LH has an obligatory role in the acute production of progesterone by the primate corpus luteum in vivo because interruption of LH support to the corpus luteum at any time during the luteal phase is accompanied by an immediate and sustained fall in serum progesterone concentrations. However, recent studies have demonstrated that maximal steroidogenic capacity of cultured human luteal cells and maximal levels of messenger RNAs (mRNAs) for cholesterol side chain cleavage cytochrome P450 (P450scc) and 3 beta-hydroxysteroid dehydrogenase, delta 5-4 isomerase (3 beta-HSD) in luteal tissue are observed shortly after luteinization and decline thereafter throughout the remainder of the luteal phase. These findings would suggest that the role of LH in the acute regulation of progesterone production may differ from its role in the expression of mRNAs for steroidogenic enzymes. We initiated the current studies to define the role of LH upon the expression of mRNAs for P450scc and 3 beta-HSD by the primate corpus luteum. For this purpose, we treated cynomolgus monkeys with a potent GnRH antagonist for 1, 2, and 3 days during the luteal phase of the menstrual cycle and measured levels of mRNAs for P450scc and 3 beta-HSD in corpora lutea. Treatment of monkeys with the GnRH antagonist reduced bioactive LH concentrations to less than 5 ng/ml by 48 h of treatment, and LH concentrations remained less than 5 ng/ml thereafter. Serum progesterone concentrations were reduced by 74% after 1 day of antagonist treatment, 88% after 2 days of antagonist treatment, and by more than 95% after 3 days of GnRH antagonist treatment. Although progesterone secretion was markedly diminished after 24 h of antagonist treatment, there were no differences in mRNAs for P450scc and 3 beta-HSD between antagonist-treated and control animals. However, mRNAs for P450scc and 3 beta-HSD were significantly (P < 0.05) reduced after 2 days of antagonist treatment and were nearly nondetectable after 3 days of antagonist treatment. These results demonstrate a temporal dissociation of the effects of LH on the acute regulation of progesterone secretion and the maintenance of specific mRNAs involved in progesterone production. Nonetheless, the results clearly show that LH is required for the continued expression of mRNAs for P450scc and 3 beta-HSD by the primate corpus luteum.

Expression of Steroid Receptors and Steroidogenic Enzymes in the Baboon (Papio anubis) Corpus Luteum during the Menstrual Cycle and Early Pregnancy1

“…7). This transcript size corresponded to the reported size for h3␤HSD in macaque CL (50,51). The message for 3␤HSD was also present in whole nonluteal ovary and in a CL obtained from a baboon treated with hCG to mimic early pregnancy.…”

In vivo responses of the primate corpus luteum to luteinizing hormone and chorionic gonadotropin

“…1 illustrates serum progesterone concentrations in three monkeys during spontaneous luteal phases (shaded area) and in three monkeys that were treated with the GnRH antagonist for 7 days, beginning on day 8 of the luteal phase. As demonstrated previously (16,17), serum progesterone concentrations fell rapidly upon administration of GnRH antagonist and were undetectable 4-5 days after the initiation of treatment. Menses occurred on days 12-14 after ovulation in the GnRH antagonist-treated animals as compared with days 15, 16, and 19 in the spontaneously cycling animals.…”

“…Comparison of the AUCs of the individual treatment groups before the initiation of the gonadotropin infusions (days 0-7) revealed that the cumulative production rates of progesterone of the animals that subsequently were treated with the exponential infusion regimen of CG were, for unexplained reasons, greater than those of the other treatment and control groups, hence the extent to which the absolute amounts of progesterone seen in this group during gonadotropin treatment may have been biased by the elevated pretreatment values is uncertain. When the data from these animals were normalized to those that received the exponentially increasing LH regimen by multiplying the day [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] AUCs by the ratio of their cumulative progesterone levels observed during days 0-7 (i.e., day 0-7 LHe͞day 0-7 CGe), the resultant normalized values for the animals that received the exponentially increasing CG regimen (61.3 Ϯ 1.76) remained statistically greater than the animals that received the exponentially increasing LH regimen but were not statistically different from the pregnant animals.…”

Identification of novel genes regulated by LH in the primate corpus luteum: insight into their regulation during the late luteal phase

“…It is well established that administration of GnRH antagonist into monkeys during mid-luteal phase leads to suppression of LH secretion and abrupt termination of the luteal phase (Ravindranath et al, 1992;Duffy et al, 1999;Fraser et al, 1999). In the present study, Cetrorelix, a synthetic GnRH antagonist, was administered s.c., at a dose of 75 mg/kg body weight twice daily (09:00 and 21:00) on day 7 of the luteal phase of the menstrual cycle.…”