Sex Steroids Mediate Bidirectional Interactions Between Hosts and Microbes

The outcome of microbial infections in mammals, including humans, is affected by the age, sex, and reproductive status of the host suggesting a role for sex steroid hormones. Testosterone, estradiol, and progesterone, signaling through their respective steroid receptors, affect the functioning of immune cells to cause differential susceptibility to parasitic, bacterial, and viral infections. Microbes, including fungi, bacteria, parasites, and viruses, can also use sex steroid hormones and manipulate sex steroid receptor signaling mechanisms to increase their own survival and replication rate. The multifaceted use of sex steroid hormones by both microbes and hosts during infection forms the basis of this review. In the arms race between microbes and hosts, both hosts and microbes have evolved to utilize sex steroid hormone signaling mechanisms for survival.     

Effects of delayed phlebotomy on plasma steroid hormone concentrations in two elasmobranch species

Measuring circulating concentrations of steroid hormones can be used as a method for determining reproductive maturity and cycles in elasmobranchs. However, it is unknown how long steroid hormones remain stable in elasmobranch blood following capture, and thus how quickly these samples should be collected for the results of subsequent steroid hormone analyses to be accurate. The objectives of this study were to determine if the sex steroid hormones progesterone, testosterone and estradiol would remain at stable concentrations in the blood of the Spiny Dogfish (Squalus acanthias Linnaeus, 1758) and the Atlantic Sharpnose Sharks (Rhizoprionodon terraenovae Richardson, 1836) that were captured, left on deck and un‐refrigerated for 24 hr. Blood samples were serially drawn from five initially live sharks over a period of 24 hr. While concentrations of all three hormones did significantly fluctuate over the sampling period in both species, the resulting hormone concentrations from each sampling period still fell within the range of previously reported values for each species in their respective reproductive stage. Additionally, no significant changes in hematocrit were detected in either species over the 24‐hr period. This research represents an extreme situation in which sharks were left on deck and un‐refrigerated, and suggests that even when subjected to these conditions steroid hormone concentrations may fluctuate, but the resulting values may still be useful for assessing reproductive stage.     

Immunochemical analysis of the interaction of the fertility alpha 2-microglobulin with steroid sex hormones

The interaction between the fertility alpha 2-microglobulin and steroid sex hormones (estrone, estriol, estradiol, progesterone, testosterone) was studied by the use of cross immunoelectrophoresis with intermediate gels. alpha 2-microglobulin was shown to bind to the above hormones, its affinity to testosterone being the highest. The ability of alpha 2-microglobulin to bind to steroid hormones can be used for its isolation by affinity chromatography with immobilized steroid hormones.     

Antecedent short-term central nervous system administration of estrogen and progesterone alters counterregulatory responses to hypoglycemia in conscious male rats

The aim of this study was to test the hypothesis that antecedent short-term administration of estradiol or progesterone into the central nervous system (CNS) reduces levels of neuroendocrine counterregulatory hormones during subsequent hypoglycemia. Conscious unrestrained male Sprague-Dawley rats were studied during randomized 2-day experiments. Day 1 consisted of an 8-h lateral ventricle infusion of estradiol (1 mug/mul; n = 9), progesterone (1 mug/mul; n = 9), or saline (0.2 mul/min; n = 10). On day 2, a 2-h hyperinsulinemic (30 pmol.kg(-1).min(-1)) hypoglycemic (2.9 +/- 0.2 mM) clamp was performed on all rats. Central administration of estradiol on day 1 resulted in significantly lower plasma epinephrine levels during hypoglycemia compared with saline, whereas central administration of progesterone resulted in increased levels of plasma norepinephrine and decreased levels of corticosterone both at baseline and during hypoglycemia. Glucagon responses during hypoglycemia were unaffected by prior administration of estradiol or progesterone. Endogenous glucose production following day 1 estradiol was significantly lower during day 2 hypoglycemia, and consequently, the glucose infusion rate to maintain the glycemia was significantly greater after estradiol administration compared with saline. These data suggest that 1) CNS administration of both female reproductive hormones can have rapid effects in modulating levels of counterregulatory hormones during subsequent hypoglycemia in conscious male rats, 2) forebrain administration of reproductive hormones can significantly reduce pituitary adrenal and sympathetic nervous system drive during hypoglycemia, 3) reproductive steroid hormones produce differential effects on sympathetic nervous system activity during hypoglycemia, and 4) reduction of epinephrine resulted in significantly blunted metabolic counterregulatory responses during hypoglycemia.     

A preliminary study of steroid reproductive hormones in human hair

Nowadays research and clinical studies of human reproductive endocrinology are generally carried out using human blood reproductive hormone assays. However the acquisition of human blood samples has some shortcomings. In search of new approaches, we paid attention to the fact that progesterone can be detected in cow's hair. Consequently we investigated whether or not steroid hormones are measurable in human hair. The results showed that the levels of steroid hormones in hair are not affected by shampoo and do not significantly vary between different segments of hair (i.e. top, middle and basal segments). The menstrual estradiol and progesterone rhythm of female hair is similar to that of female serum. The ratio of hair estradiol to serum estradiol in the female is 41.2% and that of hair progesterone to serum progesterone is 59.0%; the ratio of hair testosterone to serum testosterone in male is 116%. There are significant correlations between hair and serum steroid hormones of healthy human adult: γ (estradiol)=0.395 (n=20), p<0.05; γ (progesterone)=0.440 (n=22), p<0.025 and γ (testosterone)=0.395 (n=25), p<0.05.     

Assaying progesterone,estradiol and cortisol concentrations in hair of Père David deer hinds: an alternative way to reflect seasonality of steroid secretion

The use of a hair hormone concentration assay is increasingly recognized as a useful and noninvasive technique for monitoring the endocrinological status of animals. However, few studies have focused on reproductive and stress hormones together. We used a chemiluminescent immunoassay to determine whether the progesterone, estradiol, and cortisol concentrations could be measured from hair and whether these hormone concentrations varied in different hair segments of captive Père David deer hinds. We found that progesterone, estradiol, and cortisol could be measured in the hair samples and that the progesterone concentration varied but the estradiol and cortisol concentrations did not among different hair segments. Contrary to the segmental decline in hair cortisol found in many studies, we found that progesterone concentration was higher near the tip than at the base of hair in Père David deer. This suggests that the variation in segmental hair steroid hormone concentration in seasonal molting animals may be mainly due to internal reproductive cycles and that hair steroid hormones may reflect long-term physiological changes and can thus be used for the conservation and management of wildlife.     

Anti-fertility effects of embelin in female Sprague-Dawley rats may be due to suppression of ovarian function

Effects of embelin on oestrous cycle, plasma levels of progesterone and oestradiol, and in vitro production of oestradiol and progesterone by mixed ovarian cells was studied. Forty adult (4 months old) regularly cycling female Sprague-Dawley rats were divided into four groups of 10 rats each. Groups I and II (controls) were given 1 ml/kg body weight of physiological saline or corn oil (vehicle). Groups III and IV received 10 mg/kg and 20 mg/kg body weight embelin in corn oil, respectively. Emberlin disrupted the oestrous cycles in Groups III and IV animals, and there was a significant depression in plasma oestradiol (p <0.05) and progesterone (p <0.02) at both 10 and 20 mg/kg body weights, respectively. Isolated mixed ovarian cells from embelin treated rats produced significantly less progesterone and estradiol than controls in vitro. It is concluded that embelin probably interferes with reproductive functions in female rats by suppressing ovarian production of sex steroid hormones.     

Effects of perinatal polychlorinated biphenyls on adult female rat reproduction: development, reproductive physiology, and second generational effects

Perinatal exposures to endocrine-disrupting chemicals, such as polychlorinated biphenyls (PCBs), can cause latent effects on reproductive function. Here, we tested whether PCBs administered during late pregnancy would compromise reproductive physiology in both the fetally exposed female offspring (F1 generation), as well as in their female offspring (F2 generation). Pregnant Sprague-Dawley rats were treated with the PCB mixture, Aroclor 1221 (A1221; 0, 0.1, 1, or 10 mg/kg), on Embryonic Days 16 and 18. Somatic and reproductive development of F1 and their F2 female offspring were monitored, including ages of eye opening, pubertal landmarks, and serum reproductive hormones. The results showed that low doses of A1221 given during this critical period of neuroendocrine development caused differential effects of A1221 on F1 and F2 female rats. In both generations, litter sex ratio was skewed toward females. In the F1 generation, additional effects were found, including a significant alteration of serum LH in the 1 mg/kg A1221 group. The F2 generation showed more profound alterations, particularly with respect to fluctuations in hormones and reproductive tract tissues across the estrous cycle. On proestrus, the day of the preovulatory GnRH/gonadotropin surge, F2 females whose mothers had been exposed perinatally to A1221 exhibited substantially suppressed LH and progesterone concentrations, and correspondingly smaller uterine and ovarian weights on estrus, compared with F2 descendants of control rats. These latter changes suggest a dysregulation of reproductive physiology. Thus, low levels of exposure to PCBs during late fetal development cause significant effects on the maturation and physiology of two generations of female offspring. These findings have implications for reproductive health and fertility of wildlife and humans.     

Hormonal synchronization of the menstrual cycles of pigtail macaques to facilitate biomedical research including modeling HIV susceptibility

Background Menstrual cycle synchronization of female pigtail macaques could prove an invaluable resource in studies of the reproductive tract, associated infections, and other potential research fields. We tested whether use of an oral progesterone and estradiol combination tablet could synchronize menstrual cycles following treatment discontinuation. Methods Daily desogestrel 0.075 mg and ethinyl estradiol 0.01 mg were administered orally to three pigtail macaques at visual onset of perineal sex swelling and were continued until all animals had received it for at least 45 days. The hormones were discontinued, and these three macaques and three controls were observed for menstruation and had blood progesterone and estrogen measured over an additional 2‐month period. Results All treatment animals showed spontaneous menstrual cycle synchronization for 2 months after menstrual cycling resumed. Conclusion Progesterone and estradiol combination therapy can be used in pigtail macaques to induce synchronized cycling that persists in the absence of on‐going hormone treatments.     

Acute Effects of Sex Steroid Hormones on Susceptibility to Cardiac Arrhythmias: A Simulation Study

Acute effects of sex steroid hormones likely contribute to the observation that post-pubescent males have shorter QT intervals than females. However, the specific role for hormones in modulating cardiac electrophysiological parameters and arrhythmia vulnerability is unclear. Here we use a computational modeling approach to incorporate experimentally measured effects of physiological concentrations of testosterone, estrogen and progesterone on cardiac ion channel targets. We then study the hormone effects on ventricular cell and tissue dynamics comprised of Faber-Rudy computational models. The “female” model predicts changes in action potential duration (APD) at different stages of the menstrual cycle that are consistent with clinically observed QT interval fluctuations. The “male” model predicts shortening of APD and QT interval at physiological testosterone concentrations. The model suggests increased susceptibility to drug-induced arrhythmia when estradiol levels are high, while testosterone and progesterone are apparently protective. Simulations predict the effects of sex steroid hormones on clinically observed QT intervals and reveal mechanisms of estrogen-mediated susceptibility to prolongation of QT interval. The simulations also indicate that acute effects of estrogen are not alone sufficient to cause arrhythmia triggers and explain the increased risk of females to Torsades de Pointes. Our results suggest that acute effects of sex steroid hormones on cardiac ion channels are sufficient to account for some aspects of gender specific susceptibility to long-QT linked arrhythmias.     

Sex steroid effects at target tissues: mechanisms of action

Our understanding of the mechanisms of sex hormone action has changed dramatically over the last 10 years. Estrogens, progestins, and androgens are the steroid hormones that modulate reproductive function. Recent data have shown that many other tissues are targets of sex hormones in addition to classical reproductive organs. This review outlines new advances in our understanding of the spectrum of steroid hormone ligands, newly recognized target tissues, structure-function relationships of steroid receptors, and, finally, their genomic and nongenomic actions. Sex-based specific effects are often related to the different steroid hormone mileu in men compared with women. Understanding the mechanisms of sex steroid action gives insight into the differences in normal physiology and disease states.     

Sexual coloration, plasma concentrations of sex steroid hormones, and responses to courtship in the female keeled earless lizard (Holbrookia propinqua)

The reproductive condition, steroid hormone concentrations in the plasma, and behavior of bright and plain female Holbrookia propinqua were examined. Bright females performed significantly more aggressive rejection of courtship than plain females. Bright females were significantly more likely than plain females to have follicles larger than 5.0 mm or oviductal eggs; females with large follicles or oviductal eggs had significantly higher concentrations of progesterone and androgen than those with small follicles and lacking oviductal eggs. Plasma progesterone, androgen, and estradiol levels in the females studied behaviorally were significantly higher for the bright females than for the plain ones. Females undergoing rapid brightening were significantly more likely to be sexually receptive and copulate than were either plain or fully brightened females. The role of sex steroid hormones in coloration and behavior and the adaptive value of chromatic signalling by females are discussed.     

Bovine model for the study of reproductive aging in women: follicular, luteal, and endocrine characteristics

At present, there is no well-characterized animal model to study the effects of aging on fertility in women. The objectives of the study were to characterize age-related changes in ovarian and endocrine functions in old cows and to investigate the validity of a bovine model for the study of human reproductive aging. We tested the hypotheses that aging in cattle is associated with 1) elevated concentrations of gonadotropins and reduced concentrations of steroid hormones in systemic circulation and 2) increased recruitment of ovarian follicles during wave emergence. Daily ultrasonography was performed in 13- to 14-yr-old cows (n = 10) and their 1- to 4-yr-old daughters (n = 9) for one interovulatory interval to study ovarian function. Plasma samples were obtained every 12 h for determination of FSH, LH, progesterone, and estradiol concentrations. Circulating FSH concentrations were higher (P = 0.009) during follicular waves in old cows than in their daughters, but the number of 4- to 5-mm follicles recruited into a wave was lower (P = 0.04) in old cows. Plasma LH concentrations did not differ between groups (P = 0.4), but the ovulatory follicle in two-wave cycles was smaller in old cows (P = 0.04). Plasma estradiol concentrations were higher (P = 0.01) in old cows, and luteal phase progesterone tended to be lower (P = 0.1). We conclude that these changes are consistent with those reported for women approaching menopause transition. Therefore, our results validate the use of the bovine model to study reproductive aging in women.     

Plasma prostaglandin F2 alpha in the male Triturus carnifex (Laur.) during the reproductive annual cycle and effects of exogenous prostaglandin on sex hormones

Plasma patterns of prostaglandin F2 alpha (PGF2 alpha) and sex hormones (progesterone, androgens and 17 beta-estradiol) have been studied in the male crested newt, Triturus carnifex (Laur.), during the sexual cycle. The effects of exogenous PGF2 alpha on sex steroids have also been observed. In addition, effects of one week's captivity are reported. The patterns of plasma sex hormones, during the annual cycle, are consistent with the results previously reported for the same newt species. PGF2 alpha plasma level peaks in April, is low in summer, and progressively increases during autumn to peak again in December. The April PGF2 alpha peak coincides with a plasma estradiol increase and with an androgens drop. In April-collected newts, moreover, PGF2 alpha treatment induces a significant estradiol increase. These findings lead us to suppose that at the end of the breeding season (April) a PGF2 alpha-dependent estradiol synthesis occurs which could be implied in reproductive period termination. In several vertebrates, including some amphibian species, in fact, chronic administration of estradiol results in a strong inhibition of testicular endocrine tissue activity. The putative role of PGF2 alpha-dependent estradiol production in the gonadal regulation in amphibia living in temperate zones is discussed. The autumn PGF2 alpha increase has been tentatively related to the recovery gonadal processes and secondary sexual character development.     

Sex hormone regulation of anti-bacterial activity in rat uterine secretions and apical release of anti-bacterial factor(s) by uterine epithelial cells in culture

In mature female rats, sex hormones regulate the reproductive (estrous) cycle to optimize mating and fertility. During the part of the estrous cycle when mating occurs, and when estrogen is the dominant sex hormone, the uterus is susceptible to infection with bacteria that can be deleterious for survival and fertility. The present study investigated whether sex hormones regulate innate immunity in the female reproductive tract by affecting the secretion of an anti-bacterial factor(s) in the rat uterus. Uterine fluids from intact rats at the proestrous stage of the estrous cycle significantly inhibited Staphylococcus aureus growth. When ovariectomized rats were treated with estradiol, anti-bacterial activity against both S. aureus and Escherichia coli increased in uterine secretions with hormone treatment. In contrast, rats injected with either progesterone and estradiol or progesterone alone displayed no bactericidal activity indicating that progesterone reversed the stimulatory effect of estradiol on anti-bacterial activity. In other studies, isolated uterine epithelial cells from intact animals were grown to confluence and high transepithelial resistance on cell inserts. Analysis of apical secretions indicated that a soluble factor(s) is released by polarized epithelial cells which inhibits bacterial growth. These results demonstrate that sex hormones influence the presence of a broad-spectrum bactericidal factor(s) in luminal secretions of the rat uterus. Further these studies suggest that epithelial cells which line the uterine lumen are a primary source of anti-bacterial activity.     

Regulation of Oxidative Activity of Neutrophils by Chorionic Gonadotropin: The Role of Female Steroid Sex Hormones

We studied the effect of the main sex hormone, chorionic gonadotropin, on the production of the active forms of oxygen and nitrogen by human neutrophils and the control of its effects by female steroid sex hormones. Gonadotropin proved to inhibit both total production of oxygen metabolites and NO synthesis by the cells. Gonadotropin-dependent regulation of oxidative activity of the neutrophils is controlled by female steroid sex hormones. At the same time, progesterone completely or partially inhibits the suppressive effects of gonadotropin, while estradiol has antagonistic, sensibilizing, or permissive effect on gonadotropin depending on the dose, incubation conditions, and activation status of the cells.