Metformin: direct inhibition of rat ovarian theca-interstitial cell proliferation.

Objective: To determine whether metformin has direct effects on ovarian theca-interstitial (T-I) cell proliferation through activation of adenosine monophosphate-activated protein kinase (AMPK).

Design: In vitro experimental study.

Setting: Academic medical center laboratory.

Inhibitory effect of valproic acid on ovarian androgen biosynthesis in rat theca-interstitial cells.

The objective of the study was to evaluate the effect of valproic acid (VPA) on ovarian androgen biosynthesis in primary cultures of theca-interstitial (T-I) cells isolated from rat ovaries. Ovarian T-I cells were cultured with VPA in the presence or absence of hCG. VPA did not increase basal or hCG-stimulated androgen synthesis when added to primary cultures of T-I cells.

Evidence for the association of luteinizing hormone receptor mRNA-binding protein with the translating ribosomes during receptor downregulation.

Luteinizing hormone receptor (LHR) mRNA is post-transcriptionally regulated during ligand-induced downregulation. This process involves interaction of LHR mRNA with a specific mRNA-binding protein (LRBP), identified as mevalonate kinase (MVK), resulting in inhibition of translation followed by targeting the ribonucleoprotein complex to accelerated degradation. The present study investigated the endogenous association of LRBP with the translational machinery and its interaction with LHR mRNA during LH/hCG-induced downregulation.

The extracellular domain of luteinizing hormone receptor dictates its efficiency of maturation.

The processing of luteinizing hormone receptor (LHR) shows marked differences in different species. While the human LHR is predominantly expressed as the mature, 90kDa species, rat LHR exists mostly in the 70kDa precursor form. Since the extracellular domain of the LHR is unusually large in comparison with other G protein-coupled receptors, the present studies examined the role of extracellular domain in its processing.

Regulation of luteinizing hormone receptor mRNA expression by a specific RNA binding protein in the ovary.

The expression of LH receptor mRNA shows significant changes during different physiological states of the ovary. Previous studies from our laboratory have identified a post-transcriptional mechanism by which LH receptor mRNA is regulated following preovulatory LH surge or in response to hCG administration. A specific binding protein, identified as mevalonate kinase, binds to the open reading frame of LH receptor mRNA.

The role of luteinizing hormone/human chorionic gonadotropin receptor-specific mRNA binding protein in regulating receptor expression in human ovarian granulosa cells.

Context: In normally cycling women, LH receptor mRNA expression undergoes transient down-regulation after the LH surge. The same phenomenon is also seen during a hormonally induced ovarian cycle where the LH receptor mRNA expression is down-regulated in response to the administration of human chorionic gonadotropin (hCG). Although the granulosa cells isolated from the follicular aspirates at this stage show a decline in the expression of LH receptor mRNA, this diminished receptor expression returns to control levels upon culturing in serum-containing medium.

LH/hCG-stimulated androgen production and selective HDL-cholesterol transport are inhibited by a dominant-negative CREB construct in primary cultures of rat theca-interstitial cells.

Theca-interstitial (T-I) cells synthesize androgens that are converted to estrogen by the granulosa cells. In rat ovary, T-I cells primarily utilize HDL-derived cholesteryl esters (CE) as a precursor for androgen synthesis. The HDL-CE is delivered to steroidogenic cells by a process termed "selective" uptake in which CE is internalized without the simultaneous uptake of apolipoprotein(s).

Evidence that palmitoylation of carboxyl terminus cysteine residues of the human luteinizing hormone receptor regulates postendocytic processing.

Palmitoylation is a well-conserved posttranslational modification among members of the G protein-coupled receptor superfamily. The present study examined the role of palmitoylation in endocytosis and postendocytic trafficking of the human LH receptor (LHR). Palmitoylation of the LHR was determined by incorporation of [3H]palmitic acid into wild-type (WT) or mutant receptor in which the potential palmitoylation sites, C643 and C644, were mutated to glycine residues.

Dihydrotestosterone inhibits granulosa cell proliferation by decreasing the cyclin D2 mRNA expression and cell cycle arrest at G1 phase.

Hyperandrogenism is known to perturb ovarian physiology resulting in anovulatory conditions. In the ovary, androgens produced by theca-interstitial cells are converted to estrogens in granulosa cells under the influence of FSH and LH. In some of the target organs, including the ovary, androgens are also converted into their 5alpha reduced metabolites.

Post-transcriptional regulation of luteinizing hormone receptor mRNA in the ovary by a novel mRNA-binding protein.

Luteinizing hormone (LH) receptor mRNA is post-transcriptionally regulated. An ovarian cytosolic LH receptor mRNA-binding protein (LRBP) identified in our laboratory binds to a polypyrimidine-rich bipartite sequence in the coding region of LH receptor mRNA. The present studies show a role for LRBP in the regulation of LH receptor mRNA.