Gonadal steroid modulation of neuroendocrine transduction: A transynaptic view

Summary 1. Steroid hormones act on neuronal communication through different mechanisms, ranging from transynaptic modulation of neurotransmitter synthesis and release to development and remodeling of synaptic circuitry. Due the wide distribution of putative brain targets for steroid hormones, acute or sustained elevations of their circulating levels may affect, simultaneously, a variety of neuronal elements. In an elementary mode of interaction, steroids are able to modulate both the synthesis and release of a neurotransmitter at a particular synapse, and the response of its target postsynaptic cells. Using two neuroendocrine transducing systems—the rat pineal gland and the GT_1–7 cell line—we have examined these interactions and the following findings are discussed in this article.2. In the rat, pineal melatonin production is partially controlled by gonadal hormones. In females, melatonin synthesis and secretion is reduced during the night of proestrus, apparently as a consequence of elevated estradiol and progesterone levels. In males, circulating testosterone seems to be necessary to maintain the amplitude of the nocturnal melatonin peak.3. Some gonadal effects on pineal activity are exerted on its noradrenergic input, since changes in circulating steroid hormone levels are able to induce acute modifications of tyrosine hydroxylase activity in pineal sympathetic nerve terminals.4. Gonadal steroids are also able to regulate the response of pineal cells to adrenergic stimulation, since in vivo treatment of both male and female rats with steroid hormone blockers induces profound modifications in adrenergically-induced accumulation of cyclic AMP (cAMP) in dispersed pinealocytes.5. Direct exposure of pineal cells from gonadectomized female and male rats to estradiol (E₂) or testosterone (T), respectively, potentiates pinealocyte response to adrenergic activation. In addition, short-term (15 min) exposure to either progesterone (Pg) or progesterone coupled to bovine serum albumin (P-3-BSA) suppresses the E₂-dependent potentiation of adrenergic response in female rat pinealocytes.6. Exposure of GT_1–7 cells to E₂ completely blocked the norepinephrine (NE)-induced elevation of cAMP content. In E₂-treated GT_1–7 cells, additional exposure (15 min) to either Pg or P-3-BSA abolished E₂-dependent inhibition of NE responsiveness. In addition, P-3-BSA alone increased basal cAMP levels in GT_1–7 cells, regardless previous exposure to E₂.7. In conclusion, there are evidences, both from the current literature and from the present results, supporting the view that in some neuroendocrine systems gonadal hormones modulate neurotransmission by acting, simultaneously, at pre- and postsynaptic sites. The models presented here constitute appropriate examples of this transynaptic mode of steroid action and, therefore, may offer a useful approach to investigate steroid hormone actions on the brain.     

The effect of selected human steroid hormones upon the growth of dermatophytes with different adaptation to man

The inhibitory effect exerted by steroid hormones on thein vitro growth characteristics of dermatophytes is poorly understood. As a hypothesis this inhibition could result from fungal adaptation to the human host. Therefore, in this study the susceptibility of representative anthropophilic, zoophilic and geophilic dermatophytes to hormonal inhibition was compared. As a result, in agar dilution assaysprogesterone,testosterone, andestradiol proved to reduce fungal growth, whereashydrocortisone had no such effect. In general, anthropophilic dermatophytes were shown to be more responsive to steroid hormones than geophilic species, suggesting a correlation of steroid susceptibility with adaptation to human skin. However, since fungal response to hormones consisted of growth inhibition and occurred only at steroid concentrations much higher than present in human skin, it cannot be assumed to contribute to this adaptation.     

Estradiol regulates leptin sensitivity to control feeding via hypothalamic Cited1

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Assessing reproductive profiles in female brown mouse lemurs (Microcebus rufus) from Ranomafana National Park,southeast Madagascar,using fecal hormone analysis

Studies on reproductive endocrinology in wild primate populations have greatly increased in the last decades owing to the development of noninvasive techniques that can be applied under field conditions. However, small‐bodied nocturnal species are not well represented on the long list of primates surveyed in the wild, and reproductive inferences regarding these animals in their natural habitats have not benefited from direct observations of hormonal changes. We collected fecal samples from female brown mouse lemurs (Microcebus rufus) in a southeastern rainforest of Madagascar in order to determine whether or not fecally excreted steroid levels show a consistent pattern of change during the reproductive season and are a useful complement to reproductive observations in wild‐trapped individuals. Initial data show variation in reproductive hormone levels before and after estrus and estimated day of parturition. Elevated levels of excreted estradiol (E₂) were observed around the time of estrus, whereas high levels of fecal progesterone (P) were seen during later stages of pregnancy and around parturition. A more complete picture of reproductive profiles in female mouse lemurs, and how they may change over the life span, can be obtained if hormone analyses are used to supplement field observations. Am. J. Primatol. 71:439–446, 2009. © 2009 Wiley‐Liss, Inc.     

Serum Estradiol Correlates With Benign Paroxysmal Positional Vertigo in Postmenopausal Women

BackgroundA high incidence of benign paroxysmal positional vertigo (BPPV) is reported in postmenopausal women, and the association between estradiol (E2) deficiency and the occurrence of BPPV was investigated.MethodsPostmenopausal women with and without BPPV were included from 2016 to 2019, and 1-year follow-up was performed. Serum otolin-1 and E2 levels were assayed before the canalith repositioning treatment. Bone mineral density (BMD) was measured with a dual-energy x-ray absorptiometry scan. Receiver operating characteristic analysis was performed to determine the occurrence of BPPV, and Pearson analysis was performed to indicate the correlation between E2, otolin-1, and BMD.ResultsEighty-six postmenopausal women with BPPV and 80 age-, demographics-, and clinical characteristics-matched normal postmenopausal women were enrolled. Decreased E2 levels, increased otolin-1 levels, and decreased BMD were observed in postmenopausal women with BPPV, and increased BMD and decreased otolin-1 levels were observed in patients with higher levels of serum E2. Receiver operating characteristic analysis revealed that E2, otolin-1, and BMD showed low sensitivity and moderate specificity to determine the occurrence of BPPV. On the other hand, a low correlation coefficient was found between E2 and otolin-1, or BMD. It is worth noting that low E2 levels were found in the relapsed patients with BPPV after a 1-year follow-up.ConclusionE2 deficiency is correlated with the occurrence of BPPV, which may be a potential risk biomarker for postmenopausal women.     

Correlation of the changes of the frequency of perichromatin granules with the RNA content of the interchromatin region of uterine cells in normal and ovariectomized rats. A high resolution in situ hybridization and stereological study.

The changes in the number of perichromatin granules (PCG) and the alterations in the RNA content of the interchromatin and perichromatin regions caused by ovariectomy and estradiol injection were studied in rat endometrial fibroblast and myometrial muscle cells. Twelve rats were divided in four groups. A group of rats was fixed without any treatment, the other three groups were ovariectomized and processed 21 days after the operation. One of them was studied without further treatment, and two groups were injected intraperitoneally with 20 micrograms of 17 beta-estradiol hemisuccinate and fixed 0.5 and 2 h after the injection. The frequency of PCG was evaluated in preparations stained with EDTA procedure preferential for RNP. The alterations of RNA content were estimated by post-embedding high resolution in situ hybridization using a total DNA probe labeled with biotinilated nucleotides revealed by streptavidin coupled with 10 nm gold grains. Most of the non-nucleolar labeling is associated to RNP containing fibrils. Perichromatin and interchromatin granules are labeled to a lesser extent. Castration brings about a reduction of the number of PCG and of the numerical density of labeling in endometrial fibroblasts. The injection of estradiol causes a rapid increase in both parameters. On the contrary, the frequency of PCG and intensity of labeling of epithelial endometrial cells and in muscle cells increase after ovariectomy and are reduced by estradiol administration. These results suggest that estradiol may affect differentially various types of target cells in the same organ, and also that PCG are not the only nuclear compartment of pre-mRNA or mRNA altered by the changes in estradiol, the RNP containing fibrils located in the perichromatin and in the interchromatin regions are also involved.     

Comparison of the Subcutaneous and Intramuscular Estradiol Regimens as Part of Gender-Affirming Hormone Therapy

ObjectiveGender-affirming hormone therapy guidelines describe the estradiol (E2) doses for intramuscular (IM), but not subcutaneous (SC), routes. The objective was to compare the SC and IM E2 doses and hormone levels in transgender and gender diverse individuals.MethodsThis is a retrospective cohort study at a single-site tertiary care referral center. Patients were transgender and gender diverse individuals who received injectable E2 with at least 2 E2 measurements. The main outcomes were the dose and serum hormone levels between the SC and IM routes.ResultsThere were no statistically significant differences in age, body mass index, or antiandrogen use between patients on SC (n = 74) and those on IM (n = 56). The weekly doses of SC E2, 3.75 mg (IQR, 3-4 mg), were statistically significantly lower than those of IM E2, 4 mg (IQR, 3-5.15 mg) (P =.005); however, the E2 levels achieved were not significantly different (P =.69), and the testosterone levels were in the cisgender female range and not significantly different between routes (P =.92). Subgroup analysis demonstrated significantly higher doses in the IM group when the E2 and testosterone levels were >100 pg/mL and <50 ng/dL, respectively, with the presence of the gonads or use of antiandrogens. Multiple regression analysis demonstrated that the dose was significantly associated with the E2 levels after adjusting for injection route, body mass index, antiandrogen use, and gonadectomy status.ConclusionBoth the SC and IM E2 achieve therapeutic E2 levels without a significant difference in the dose (3.75 vs 4 mg). SC may achieve therapeutic levels at lower doses than IM .     

Photobiomodulation and estrogen stabilize mitochondrial membrane potential in angiotensin–II challenged porcine aortic smooth muscle cells

Rupture of Abdominal aortic aneurysm (AAA) is among the 15 leading causes of death after age 65. Using high frequency ultrasound, we showed that photobiomodulation (PBM) prevents formation and progression of AAA in the angiotensin-II (Ang-II)-infused, apolipoprotein-e-deficient mouse model. In the current study we report that while challenge of porcine aortic Smooth Muscle Cells (SMCs) with Ang-II (1 μM) resulted in a marked decay in mitochondrial membrane potential (MitMP) vs non-challenged cells, treatment with PBM (continuous diode laser, 780 nm, 6.7 mW/cm², 5 minutes, 2 J/cm²) or pre-incubation with estrogen (50 nM, 1 hour) significantly attenuated this deterioration in MitMP. We also report that PBM and estrogen markedly affected porcine aortic SMC contraction and modified mitochondrial dispersion reflecting important influence on SMC function. These studies provide strong evidence of the important underlying role of mitochondria in the preventive effect of PBM on formation and progression of AAA and its reduced incidence and delayed onset in women.