Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acetyl-L-carnitine (ALC) is known to affect several aspects of neuronal activity. To evaluate the neuroendocrine actions of this compound, several endocrinological parameters were followed in ALC-treated and control animals during recovery from dark-induced anestrus. In treated animals, serum luteinizing hormone (LH) and prolactin levels were higher than those of controls during the proestrous and estrous phases of the cycle, and serum estradiol levels were higher during estrus. No significant changes were observed in serum levels of follicle-stimulating hormone and progesterone. Uterine weight was increased in ALC-treated rats during proestrus and estrus, but not in diestrus. The basal release of gonadotropin-releasing hormone (GnRH) from perifused hypothalamic slices of ALC-treated animals was elevated at proestrus and diestrus, and GnRH release elicited by high K+ was higher during all three phases of the cycle. The basal release of LH from perifused pituitaries of treated animals was elevated in diestrus, and the LH response to GnRH was higher in estrus and diestrus I. Depolarization with K+ caused increased LH secretion during proestrus and estrus in treated animals. In contrast to these effects of ALC treatment in vivo, no direct effects of ALC were observed during short- or long-term treatment of cultured pituitary cells. These results indicate that ALC treatment influences hypothalamo-pituitary function in a cycle stage-dependent manner, and increases the secretory activity of gonadotrophs and lactotrophs. Since no effects of ALC on basal and agonist-induced secretory responses of gonadotrophs were observed in vitro, it is probable that its effects on gonadotropin release are related to enhancement of GnRH neuronal function in the hypothalamus.
J Steroid Biochem Mol Biol 1992 Oct
PMID:Actions of acetyl-L-carnitine on the hypothalamo-pituitary-gonadal system in female rats. 139 Feb 85

A luteinising hormone receptor binding inhibitor (LHRBI) has been purified from bovine corpus luteum (CL). Steroid-free extract of the CL was subjected to successive chromatographies on Sephadex G-50, Q-Sepharose, Orange A dye and metal chelate affinity columns followed by high performance-reverse phase and gel filtration columns. Purification was monitored by the ability of the fractions to inhibit the binding of 125I-human chorionic gonadotropin (hCG) to porcine granulosa cells in vitro. The final isolate showed an 8000-fold enrichment of activity. It was also capable of inhibiting porcine granulosa cell secretion of estradiol and progesterone (P) in vitro. Administration of LHRBI into follicle-stimulating hormone (FSH)-stimulated, immature rats strongly inhibited the ovarian ovulatory response to hCG as revealed by decreased P levels and the number of ova released. The M(r) of LHRBI as assessed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis was ca. 15 kDa and the pI was between 5.0 and 5.5.
Mol Cell Endocrinol 1992 Sep
PMID:Isolation of luteinising hormone receptor binding inhibitor from bovine corpus luteum. 144 83

The receptor binding surface of human follicle-stimulating hormone (hFSH) is mimicked by synthetic peptides corresponding to the hFSH-beta chain amino acid sequences 33-53 [Santa-Coloma, T. A., Dattatreyamurty, D., and Reichert, L. E., Jr. (1990), Biochemistry 29, 1194-1200], 81-95 [Santa-Coloma, T. A., Reichert, L. E., Jr. (1990), J. Biol. Chem. 265, 5037-5042], and the combined sequence (33-53)-(81-95) [Santa-Coloma, T. A., Crabb, J. W., and Reichert, L. E., Jr. (1991), Mol. Cell. Endocrinol. 78, 197-204]. These peptides have been shown to inhibit binding of hFSH to its receptor. Circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopy were used to determine the structure of the first peptide in this series, the 21 amino acid peptide hFSH-beta-(33-53), H2N-YTRDLVYKDPARPKIQKTCTF-COOH. Analysis of CD data indicated the presence of approximately equal amounts of antiparallel beta-pleated sheet, turns including a beta-turn, "other" structures, and a small amount of alpha-helix. The major characteristics of the structure were found to be relatively stable at acidic pH and the predominant effect of increased solvent polarity was a small increase in alpha-helical content. One- and two-dimensional NMR techniques were used to obtain full proton and carbon signal assignments in aqueous solution at pH 3.1. Analysis of NMR results confirmed the presence of the structural features revealed by CD analysis and provided a detailed picture of the secondary structural elements and global folding pattern in hFSH-beta-(33-53). These features included an antiparallel beta-sheet (residues 38-51 and 46-48), turns within residues 41-46, and 50-52 (a beta-turn) and a small N-terminal helical region comprised of amino acids 34-36. One of the turns is facilitated by prolines 42 and 45. Proline-45 was constrained to the trans conformation, whereas proline-42 favored the trans conformer (approximately 70%) over the cis (approximately 30%). Two resonances were observed for the single alanine residue (A-43) sequentially proximal to P-42, but the rest of the structure was minimally affected by the isomerization at proline-42. The major population of molecules, containing trans-42 and trans-45 prolines, presented 120 NOEs. Distance geometry calculations with 140 distance constraints and energy minimization refinements were used to derive a moderately well-defined model of the peptide's structure.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Solution structure of a synthetic peptide corresponding to a receptor binding region of FSH (hFSH-beta 33-53). 144 99

Previous studies have shown that basic fibroblast growth factor (bFGF) can modulate basal and luteinizing hormone/human chorionic gonadotropin (LH/hCG)-stimulated Leydig cell functions. It has not been ascertained whether these actions are due to direct or indirect effects on Leydig cells. To resolve this question, a multi-step procedure was used to isolate highly-purified Leydig cells from immature rats. 125I-bFGF binding studies were performed on cultured cells. Scatchard analysis of the data indicated a single binding site with an apparent Kd of 82 pM and a binding capacity of approximately 2800 sites per cell. Both bFGF and acidic FGF similarly were effective in displacing 125I-bFGF, suggesting that the receptor binds both bFGF and aFGF. However, neither hCG, follicle-stimulating hormone (FSH), insulin, insulin-like growth factor-1 (IGF-1), prolactin, platelet-derived growth factor (PDGF) or epidermal growth factor (EGF) were effective competitors. When binding studies were conducted on cultured testicular interstitial cellular fractions that are normally discarded during Leydig cell purification, bFGF receptors were identified in these fractions. These results demonstrate that bFGF can have direct effects on Leydig cells through specific receptors; however, because other interstitial cell type(s) also have bFGF receptors, they stress the importance of using highly purified cells when evaluating bFGF actions on Leydig cells.
Mol Cell Endocrinol 1992 Oct
PMID:Evidence for basic fibroblast growth factor receptors in cultured immature Leydig cells. 145 39

The major ganglioside NeuAc alpha 2-->3Gal beta 1-->4Glc beta 1-->1Cer (GM3) present in cultured rat granulosa cells was examined for potential function in the expression of luteinizing hormone (LH) receptor on the cell surface in response to follicle-stimulating hormone (FSH). Synthesis of GM3 was stimulated concentration-dependently by FSH, and the stimulation was enhanced synergistically by insulin, as revealed by metabolic labeling of glycosphingolipids with [3H]galactose. When granulosa cells were cultured in the media containing GM3 (0.2-20 microM), biphasic changes in FSH-dependent expression of LH receptor were observed, as measured by the binding of 125I-deglycosylated human choriogonadotropin to the intact cells. Exogenous GM3 suppressed expression of LH receptor in the cells treated with a low dose of FSH (20 ng/ml), which was characterized by a low GM3 level, to 30% of control at 10 microM, with a half-maximal inhibitory concentration of 8 microM. In contrast, in the cells treated with a high dose of FSH (100 ng/ml) and insulin, which was characterized by a high GM3 level, expression of LH receptor was enhanced by exogenous GM3, to 148% of control at 10 microM, with a half-maximal effective concentration of 2 microM. Exogenous GM3 produced concomitant changes in the levels of extracellular cAMP. These effects of exogenous GM3 were not accompanied by changes in granulosa cell proliferation. Exogenous GM3 also modulated the LH receptor expression by the synergistic action of 12-O-tetradecanoylphorbol 13-acetate with insulin, with no significant changes in cellular DNA contents, suggesting that exogenous GM3 does not modulate directly the action of FSH at its receptor sites.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1992 Oct
PMID:Biphasic effects of exogenous ganglioside GM3 on follicle-stimulating hormone-dependent expression of luteinizing hormone receptor in cultured granulosa cells. 145 40

The putative promoter regions of the murine follicle-stimulating hormone (FSH) and luteinizing hormone (LH) receptor genes were isolated and used to map transcription initiation sites for both genes. For the FSH receptor gene, a major transcription initiation site was found 534 nucleotides upstream, and for the LH receptor gene 310 nucleotides upstream of the corresponding translation initiation codons. In addition, several alternative minor transcription initiation sites were observed for both genes. The nucleotide sequences of the promoter regions revealed no canonical promoter elements, such as TATA and CCAAT consensus sites 5' of the main transcriptional start sites. The isolated promoter segments for both receptor genes showed low functional activity as verified in transient expression studies in immature rat granulosa cells using the luciferase coding region as the reporter for promoter activity. Both promoter elements seem to be still under tissue specific control, since neither LH receptor nor FSH receptor promoter activity was detectable in another cell line (CHO) investigated.
Mol Cell Endocrinol 1992 Oct
PMID:The murine luteinizing hormone and follicle-stimulating hormone receptor genes: transcription initiation sites, putative promoter sequences and promoter activity. 145 41

Prodynorphin is expressed by neurons of the hypothalamus and gonadotrophs of the anterior pituitary gland (AP) and plays a role in the negative feedback regulation of the reproductive neuroendocrine axis. The present study examined whether gonadal steroid hormones are capable of modulating pituitary prodynorphin expression in immature, female rats. Steroids were administered via subcutaneous Silastic implants and rats were killed at 29 days of age. Northern blot analysis was used to measure AP prodynorphin, luteinizing hormone-beta (LH beta), follicle-stimulating hormone-beta (FSH beta), and common alpha-subunit mRNA levels (normalized to 18S ribosomal RNA). Treatment groups (n = 5-6) consisted of control (CNT; empty implants), estradiol (E2; 4 days), E2 + progesterone (E2 + P4; 8 days and 4 days, respectively), and dihydrotestosterone (DHT; 4 days). Pituitary prodynorphin mRNA was significantly suppressed in only the DHT-treated animals (26 +/- 10% of CNT, p < 0.01). LH beta mRNA was suppressed by all steroid treatments (p < 0.01), FSH beta was lower in only the E2 group, and alpha-subunit was reduced in both the E2 + P4 and DHT groups (p < 0.01). Serum LH was suppressed by all steroid treatments but FSH was reduced in only the E2 and E2 + P4 groups (p < 0.01). Treatment of prepubescent rats with continuous high levels of gonadal steroids is known to severely reduce endogenous hypothalamic gonadotropin releasing hormone (GnRH) release and this is supported by our observation of reduced gonadotropin-subunit gene expression.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1992 Oct
PMID:Differential regulation of anterior pituitary prodynorphin and gonadotropin-subunit gene expression by steroid hormones. 145 42

Pig granulosa cells have been shown to synthesize insulin-like growth factor (IGF) I peptide in vitro, and this expression is regulated by gonadotropins via the cAMP pathway. By hybridizing an IGF I cDNA probe with total RNA isolated from pig granulosa cells cultured in vitro, we show that these cells contain two IGF I transcripts of about 0.9 kb and 9 kb in size. Treatment of the cells with gonadotropins (follicle-stimulating hormone, luteinizing hormone) or cAMP agonists (dibutyryl-cAMP, forskolin) induces an accumulation of the transcripts which can be abolished by transcriptional inhibitors, but not by translational inhibitors. We thus provide new evidence that pig granulosa cells are a site of IGF I synthesis, and we conclude that (1) gonadotropins increase IGF I mRNA levels; (2) the accumulation of IGF I mRNA results from an increased transcription; (3) the stimulation of IGF I gene transcription does not require ongoing protein synthesis; (4) these effects of follicle-stimulating hormone can be mimicked by cAMP agonists.
Mol Cell Endocrinol 1992 Aug
PMID:Gonadotropins induce accumulation of insulin-like growth factor I mRNA in pig granulosa cells in vitro. 151 89

In vitro and in vivo release of pituitary hormones were studied in the presence of (hydroxyproline9)LHRH ((Hyp)LHRH), a newly characterized endogenous molecular form of LHRH. Results were compared to those obtained with LHRH itself. (Hyp)LHRH, as LHRH, stimulated both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release in a homothetic manner. The hydroxylated compound was, however, 24 times (in vitro) and 5 times (in vivo) less potent than LHRH. The lower activity of (Hyp)LHRH than of LHRH in the in vitro assay correlated well with a 28-fold lesser potency in a binding test using pituitary membrane preparations. The higher relative potency and the prolonged effect of (Hyp)LHRH in the in vivo test were related to a lesser susceptibility of the hydroxylated form to proteolytic degradation. Effects of LHRH and of (Hyp)LHRH were not additive, both peptides were equally able to desensitize gonadotrophs to a subsequent challenge by the other. Taken together, these observations suggest that both forms of LHRH act at the same receptor site. The lesser affinity of the hydroxylated compound is compensated to a certain extent by its higher resistance to enzymatic degradation. It is concluded that in spite of its lesser potency, (Hyp)LHRH may participate in the regulation of gonadotropins.
Mol Cell Endocrinol 1992 May
PMID:A second endogenous molecular form of mammalian hypothalamic luteinizing hormone-releasing hormone (LHRH), (hydroxyproline9)LHRH, releases luteinizing hormone and follicle-stimulating hormone in vitro and in vivo. 152 18

Recent studies have suggested that growth hormone-releasing factor (GRF), like vasoactive intestinal peptide (VIP), may enhance follicle-stimulating hormone (FSH)-stimulated steroidogenesis in cultured rat granulosa cells (GC). Because effects of GRF or VIP on GC proliferation have not been reported, we evaluated and compared the effect of GRF to that of VIP using cultured bovine GC. Undifferentiated GC from 1-5 mm bovine follicles were established for 2 days in medium containing 10% fetal calf serum, washed and then cultured in chemically defined medium for an additional 2 days. Two-day treatment with 2.5-1000 ng/ml of VIP had no effect (P greater than 0.05) on proliferation or progesterone production of bovine GC in the presence or absence of 200 ng/ml FSH. In comparison, 100, 250, 500, 1000 or 2000 pg/ml of human [desNH2Tyr1,D-Ala2,Ala15]-GRF(1-29)-NH2 analog caused a dose-dependent stimulation (P less than 0.05) of GC proliferation in the absence and presence of 5 micrograms/ml insulin. However, the GRF analog had no effect (P greater than 0.05) on GC progesterone production (expressed as ng/10(5) cells/24 h) in the absence or presence of 5 micrograms/ml insulin. The effects of GRF analog on progesterone production and cell proliferation were not influenced by co-culture with 200 ng/ml FSH. GRF(1-44)-NH2 also stimulated cell proliferation but had no effect on basal or FSH-induced progesterone production. These results suggest that GRF may play a role in GC proliferation during follicular development in the bovine.
Mol Cell Endocrinol 1992 Jan
PMID:Effects of growth hormone-releasing factor and vasoactive intestinal peptide on proliferation and steroidogenesis of bovine granulosa cells. 155 71


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