Leptin inhibits gonadotrophin-stimulated granulosa cell progesterone production by antagonizing insulin action. 1999

J D Brannian, and Y Zhao, and M McElroy
Department of Obstetrics and Gynecology, University of South Dakota School of Medicine, 1400 West 22nd Street, Sioux Falls, SD 57105-1570, USA.

Recent evidence has demonstrated that expression of leptin and leptin receptors is expected in the human ovary, and that leptin alters ovarian steroidogenesis in animal models. This study was designed to determine whether leptin modulates basal, gonadotrophin-, and insulin-stimulated progesterone production by human luteinized granulosa cells (GC). GC were recovered from follicular aspirates obtained during transvaginal ultrasound-guided oocyte retrieval for in-vitro fertilization-embryo transfer, and cultured in defined medium with various combinations of chorionic gonadotrophin (HCG; 0 or 100 ng/ml), insulin (0-30 microg/ml), and leptin (0-100 ng/ml). Progesterone concentrations in media were determined at various time points (2 h to 6 days). Leptin time- and dose-dependently inhibited (P < 0.05) HCG-stimulated progesterone production by human luteinized GC, but did not alter basal steroidogenesis. Moreover, the inhibitory effect of leptin on gonadotrophin-stimulated progesterone production was only manifested in the presence of insulin. Leptin suppression of insulin-supported steroidogenesis was also time- and dose-dependent. We conclude that leptin inhibits gonadotrophin-stimulated GC progesterone production apparently by antagonizing insulin action. Leptin suppression of progesterone production by human luteinized GC is consistent with recent data from animal models, and supports the possible role of leptin as a regulator of human ovarian function.

UI MeSH Term Description Entries
D007328 Insulin A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1). Iletin,Insulin A Chain,Insulin B Chain,Insulin, Regular,Novolin,Sodium Insulin,Soluble Insulin,Chain, Insulin B,Insulin, Sodium,Insulin, Soluble,Regular Insulin
D007329 Insulin Antagonists Compounds which inhibit or antagonize the biosynthesis or action of insulin. Antagonists, Insulin
D011374 Progesterone The major progestational steroid that is secreted primarily by the CORPUS LUTEUM and the PLACENTA. Progesterone acts on the UTERUS, the MAMMARY GLANDS and the BRAIN. It is required in EMBRYO IMPLANTATION; PREGNANCY maintenance, and the development of mammary tissue for MILK production. Progesterone, converted from PREGNENOLONE, also serves as an intermediate in the biosynthesis of GONADAL STEROID HORMONES and adrenal CORTICOSTEROIDS. Pregnenedione,Progesterone, (13 alpha,17 alpha)-(+-)-Isomer,Progesterone, (17 alpha)-Isomer,Progesterone, (9 beta,10 alpha)-Isomer
D011506 Proteins Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein. Gene Products, Protein,Gene Proteins,Protein,Protein Gene Products,Proteins, Gene
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D004624 Embryo Transfer The transfer of mammalian embryos from an in vivo or in vitro environment to a suitable host to improve pregnancy or gestational outcome in human or animal. In human fertility treatment programs, preimplantation embryos ranging from the 4-cell stage to the blastocyst stage are transferred to the uterine cavity between 3-5 days after FERTILIZATION IN VITRO. Blastocyst Transfer,Tubal Embryo Transfer,Tubal Embryo Stage Transfer,Embryo Transfers,Transfer, Embryo,Transfers, Embryo
D005260 Female Females
D005307 Fertilization in Vitro An assisted reproductive technique that includes the direct handling and manipulation of oocytes and sperm to achieve fertilization in vitro. Test-Tube Fertilization,Fertilizations in Vitro,In Vitro Fertilization,Test-Tube Babies,Babies, Test-Tube,Baby, Test-Tube,Fertilization, Test-Tube,Fertilizations, Test-Tube,In Vitro Fertilizations,Test Tube Babies,Test Tube Fertilization,Test-Tube Baby,Test-Tube Fertilizations
D006063 Chorionic Gonadotropin A gonadotropic glycoprotein hormone produced primarily by the PLACENTA. Similar to the pituitary LUTEINIZING HORMONE in structure and function, chorionic gonadotropin is involved in maintaining the CORPUS LUTEUM during pregnancy. CG consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is virtually identical to the alpha subunits of the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity (CHORIONIC GONADOTROPIN, BETA SUBUNIT, HUMAN). Chorionic Gonadotropin, Human,HCG (Human Chorionic Gonadotropin),Biogonadil,Choriogonadotropin,Choriogonin,Chorulon,Gonabion,Human Chorionic Gonadotropin,Pregnyl,Gonadotropin, Chorionic,Gonadotropin, Human Chorionic
D006107 Granulosa Cells Supporting cells for the developing female gamete in the OVARY. They are derived from the coelomic epithelial cells of the gonadal ridge. Granulosa cells form a single layer around the OOCYTE in the primordial ovarian follicle and advance to form a multilayered cumulus oophorus surrounding the OVUM in the Graafian follicle. The major functions of granulosa cells include the production of steroids and LH receptors (RECEPTORS, LH). Cell, Granulosa,Cells, Granulosa,Granulosa Cell

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