Multihormonal regulation of progesterone synthesis in cultured human midluteal cells.

Abstract

The objectives of this investigation were to examine in vivo insulin like-growth factor-I (IGF-I) secretion by the human midcorpora lutea (mid-CL) and the effects of IGF-I, hCG, FSH, and human GH on progesterone (P) production by CL cells obtained from patients at laparotomy. We first examined whether the CL produces IGF-I by measuring IGF-I levels in the ovarian vein from the ovary bearing the CL. The IGF-I concentration in the ovarian vein bearing the CL (206 +/- 31 ng/mL) was significantly increased compared to the concentration in the contralateral ovarian vein (179.2 +/- 32 ng/mL; P < 0.05). Luteal cells isolated from mid-CL were cultured in serum-free medium 199 in the presence and absence of hCG, FSH, GH, and graded concentrations of IGF-I. At the end of the incubation period (24 h), P levels in the medium were measured by RIA. The treatment with IGF-I (0.1-10 ng/mL) showed a dose-dependent stimulatory action of IGF-I on P synthesis in the luteal cell system, being maximal between 5-10 ng/mL. The treatment with hCG (10 IU/mL), IGF-I (5 ng/mL), and GH (1000 ng/mL) increased basal P synthesis by 300%, 80%, and 30%, respectively (P < 0.001 and P < 0.05). FSH (100 ng/mL), either alone or in combination with IGF-I, failed to stimulate P synthesis. Treatment with IGF-I monoclonal antibody (1:5000) completely reduced P synthesis induced by 5 ng/mL IGF-I and slightly reduced basal P synthesis as well as GH-stimulated P synthesis by human midluteal cells. To further evaluate the specific role of IGF-I on luteal steroidogenesis, IGF-I receptor was identified by chemical cross-linking of [125I]IGF-I to mid-CL membranes. Experiments conducted in the absence and presence of unlabeled IGF-I (500 ng) revealed proteins with characteristics of the type I IGF receptor. These results are consistent with multihormonal regulation of P synthesis by the human mid-CL. hCG and IGF-I play a major role in the stimulation of P synthesis and, to a lesser extent, human GH. These in vivo and in vitro data suggest that the CL is a site of secretion, action, and reception of IGF-I during the midluteal phase.

Effect of nitric oxide on the expression of insulin-like growth factors and the insulin-like growth factor binding proteins throughout the lifespan of the human corpus luteum

“…Functional studies have shown that IGF-I stimulates progesterone production by the rat corpus luteum (Parmer et al, 1991), which increases when the cells are stimulated simultaneously with IGF-I and hCG (Talavera and Menon, 1991). Similar results have been reported in human luteal cells, in which IGF-I enhances both basal and hCG-stimulated progesterone production (Devoto et al, 1995). In addition, IGF-I induces an increase in oestradiol secretion by human luteinized granulosa cells and by luteal cells in culture (Erickson et al, 1989;Johnson et al, 1996).…”

“…Tissue explants (three corpora lutea from the early luteal phase, n = 8 slices; five corpora lutea from the mid-luteal phase, n = 12 slices; and four corpora lutea from the late luteal phase, n = 10 slices) were treated with L-Arginine (1 mmol l -1 ) forIGF receptor was not addressed directly in the present study, although the data indicate that the binding proteins and the receptor regulate the metabolic actions of IGFs in corpora lutea from the mid-luteal phase. IGF-I exerts a luteotrophic action by stimulating progesterone and oestradiol synthesis in cultures of luteal cells from the midluteal phase (Devoto et al, 1995;Niswender et al, 2000).…”

Growth hormone and insulin-like growth factor-I action on progesterone secretion by porcine corpora lutea isolated at various periods of the luteal phase

“…Using human luteal cells from early and mid-luteal phase of the menstrual cycle, Apa et al (1996) found that IFG-I was able to stimulate directly production of progesterone and additionally mediated the positive action of GH on progesterone synthesis. Measuring IGF-I production by the CL and then synergistic action with GH, FSH and hCG on progesterone secretion, Devoto et al (1995) suggested that human CL is a site of secretion, action and reception of IGF-I during the mid-luteal phase.…”

Expression of Steroidogenic Acute Regulatory Protein in the Human Corpus Luteum throughout the Luteal Phase

“…Three women undergoing tubal ligation were administered Cetrorelix (2 mg, sc; ASTA Medica AWD GmnH, Frankfurt, Germany) during the midluteal phase 24 h before surgery. Plasma LH and progesterone were determined by specific RIA as previously reported (5). These studies were approved by the internal review board of the Hospital Clinico San Borja Arriarán.…”