Biomedical subjects

Jose M Soares

Publications and source records attributed to Jose M Soares.

3 recordsLinked to original sources

PubMed2005

17Beta-estradiol modulates hMT1 melatonin receptor function.

Estrogen modulates expression and function of G-protein-coupled receptors. The goal of this study was to assess the effect of 17beta-estradiol (10 nM) exposure for 1 (E1) or 6 (E6) days on density and function of hMT1 and hMT2 melatonin receptors expressed in Chinese hamster ovary (CHO) cells (CHO-MT1/CHO-MT2 cells). This strain of CHO cells expressed both estrogen receptor alpha and beta mRNAs, as determined by RT-PCR amplification. 17beta-Estradiol treatment did not modify the affinity of either receptor; however, it significantly increased the density of 2-[125I]iodomelatonin-binding sites in CHO-MT2 cells. 17beta-Estradiol treatment (1-6 days) did not affect the potency of melatonin to inhibit forskolin stimulation of cAMP formation through activation of either MT1 or MT2 receptors; however, it significantly attenuated the maximal inhibition of forskolin-stimulated cAMP formation induced by melatonin (0.01-1 microM) in CHO-MT1 cells. Melatonin stimulation of [35S]GTPgammaS binding to CHO-MT1 cell membranes was also attenuated following estradiol treatment. The inverse agonist luzindole reduced basal [35S]GTPgammaS binding in estradiol-treated cells but not in control CHO-MT1 cells, suggesting that estradiol promotes constitutive activity of MT1 melatonin receptors. We suggest that 17beta-estradiol differentially affects MT1 and MT2 melatonin receptor functions, attenuates melatonin responses through activation of MT1 receptors, and increases the MT2 receptors density.

Analysis of Variance↗

PubMed2003

Functional melatonin receptors in rat ovaries at various stages of the estrous cycle.

This study investigated the receptor mechanism(s) by which the hormone melatonin directly affects ovarian function. Expression of MT1 and MT2 melatonin receptor mRNA was detected in the rat ovaries both by reverse transcriptase-polymerase chain reaction and in situ hybridization with digoxigenin-labeled oligoprobes. Specific 2-[125I]iodomelatonin binding was significantly higher in ovarian tissue from animals sacrificed during proestrus than in metestrus, suggesting regulation of melatonin receptors by estrogens. Additionally, basal and melatonin-mediated stimulation of guanosine 5'-O-(3-[35S]thio)triphosphate ([35S]GTPgammaS) binding to ovarian sections was higher in proestrus compared with metestrus. During proestrus, both luzindole (0.1 microM) and 4-phenyl-2-propionamidotetraline (4P-PDOT) (0.1 microM), acting as inverse agonists, inhibited basal [35S]GTPgammaS binding to ovarian sections, suggesting the presence of MT1 constitutively active melatonin receptors. In primary cultures of ovarian granulosa cells, melatonin inhibited forskolin-stimulated cAMP accumulation through activation of Gi-coupled melatonin receptors. This inhibition was blocked by both, luzindole, and 4P-PDOT, acting as competitive receptor antagonists. Exposure of granulosa cells in culture to 17beta-estradiol seems to alter the state of melatonin receptor coupling. Indeed, the efficacy of 4P-PDOT on forskolin-stimulated cAMP formation was reversed from an MT2 partial agonist in vehicle-treated cells to that of an MT1 inverse agonist in 17beta-estradiol (0.1 microM)-treated granulosa cells. We conclude that MT1 and MT2 melatonin receptors expressed in antral follicles and corpus luteum may affect steroidogenesis through cAMP-mediated signaling. These results underscore the implications of the levels of ovarian estrogen when melatonin receptor ligands are used as therapeutic agents.

Animals↗

PubMed2002

Benefits of soy isoflavone therapeutic regimen on menopausal symptoms.

OBJECTIVE: To examine the change in menopausal symptoms and cardiovascular risk factors in response to 4 months of daily 100-mg soy isoflavone in postmenopausal women. METHODS: In this double-blind, placebo-controlled study, 80 women were randomly assigned to isoflavone (n = 40) and placebo (n = 40) treatment. The menopausal Kupperman index was used to assess change in menopausal symptoms at baseline and after 4 months of treatment. Cardiovascular risk factors were assessed by evaluating plasma lipid levels, body mass index, blood pressure, and glucose levels in the participants. To examine the effects of this regime on endogenous hormone levels, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and 17 beta-estradiol were measured. Transvaginal sonography was performed to quantify endometrial thickness. RESULTS: The data showed a decrease in menopausal symptoms (P <.01, paired t test, two-tailed, between baseline and isoflavone groups, and P <.01, unpaired t test, between placebo and isoflavone groups). Total cholesterol and low-density lipoprotein decreased significantly in the isoflavone group compared with the baseline or placebo group (P <.001, paired t test, two-tailed, between baseline and isoflavone groups, and P <.01, unpaired t test, between placebo and isoflavone groups). The isoflavone treatment appeared to have no effect on blood pressure, plasma glucose, and high-density lipoprotein and triglyceride levels. CONCLUSION: This study suggests that isoflavone 100-mg regime treatment may be a safe and effective alternative therapy for menopausal symptoms and may offer a benefit to the cardiovascular system.

Blood Glucose↗