Journal of steroids & hormonal science最新文献

Background: A number of physiological factors have been suggested to participate in the alpha- Human Herpesvirus (αHHV) reactivation, such as hormonal aberration. Thyroid hormone (TH) was shown to play a suppressive role in Herpes Simplex Virus Type-1 (HSV-1) gene expression and replication in cell culture and animal models. We hypothesize that reactivation of αHHV in humans may be due to, at least in part, by TH status.

Methods: Prior to implementing a full-scale population-based prospective inquiry into this hypothesis, a pilot study using a medical claims data base and a case-controlled, retrospective cohort investigation was conducted to develop a hypothetical link between TH complication and αHHV reactivation. Using diagnostic codes for treating thyroid disorders and αHHV infections as proxies for biologic/clinic outcomes, we queried a large, comprehensive hospital data base to construct two patient cohorts: Cohort 1 was comprised of patients receiving TH diagnoses over a twelve-year period, and Cohort 2 was composed of patients not receiving TH diagnoses during this period. Diagnoses of αHHV were recorded for each cohort and the difference in the frequency was examined for statistical significance. Demographic analyses such as age, gender, etc were also performed.

Results: Using 2×2 contingency table analyses and Statistical Analysis Software (SAS), an Odds Ratio (OR) of 2.83 was observed for the total population of 21 years old and above with a chi-square of 61.55 and p < 0.001, confirming that a severe significant difference was found between these two cohorts. This result suggested that patients with αHHV diagnosis have higher chances to have TH disorders. Additional investigation revealed that female were at higher/significant probability to have both TH and αHHV diagnosis, indicating a link of αHHV reactivation to a complex hormonal profile difference between genders. Our observation indicated that female patients of 21 years of age and above exhibited a very high incidence (OR of 3.40, p < 0.001) compared to the male groups (OR of 1.91, p < 0.05), indicating the possibility that hormonal alteration in females maybe transient but robust and can lead to αHHV reactivation more often than the males.

Conclusion: These results indicated that TH dysfunction may have implication in αHHV pathogenesis and females exhibited much higher probability to suffer αHHV reactivation due to TH disruption. Although the results from this pilot study have limitations and require additional controlled clinical examination such as more detailed patient records, lab data, therapeutic outcome, etc, it provides a tool to assess the effects of hormone imbalance on virus reactivation by retrospective analyses using existing large scale data base.

Objective: Progesterone (P₄) plays a central role in women's health. Synthetic progestins are used clinically in hormone replacement therapy (HRT), oral contraceptives, and for the treatment of endometriosis and infertility. Unfortunately, synthetic progestins are associated with side effects, including cardiovascular disease and breast cancer. Botanical dietary supplements are widely consumed for the alleviation of a variety of gynecological issues, but very few studies have characterized natural compounds in terms of their ability to bind to and activate progesterone receptors (PR). Kaempferol is a flavonoid that functions as a non-steroidal selective progesterone receptor modulator (SPRM) in vitro. This study investigated the molecular and physiological effects of kaempferol in the ovariectomized rat uteri.

Methods: Since genistein is a phytoestrogen that was previously demonstrated to increase uterine weight and proliferation, the ability of kaempferol to block genistein action in the uterus was investigated. Analyses of proliferation, steroid receptor expression, and induction of well-established PR-regulated targets Areg and Hand2 were completed using histological analysis and qPCR gene induction experiments. In addition, kaempferol in silico binding analysis was completed for PR. The activation of estrogen and androgen receptor signalling was determined in vitro.

Results: Molecular docking analysis confirmed that kaempferol adopts poses that are consistent with occupying the ligand-binding pocket of PRA. Kaempferol induced expression of PR regulated transcriptional targets in the ovariectomized rat uteri, including Hand2 and Areg. Consistent with progesterone-l ke activity, kaempferol attenuated genistein-induced uterine luminal epithelial proliferation without increasing uterine weight. Kaempferol signalled without down regulating PR expression in vitro and in vivo and without activating estrogen and androgen receptors.

Conclusion: Taken together, these data suggest that kaempferol is a unique natural PR modulator that activates PR signaling in vitro and in vivo without triggering PR degradation.