Genetic Etiology of Idiopathic Hypogonadotropic Hypogonadism

Idiopathic hypogonadotropic hypogonadism (IHH) is a group of rare developmental disorders characterized by low gonadotropin levels in the face of low sex steroid hormone concentrations. IHH is practically divided into two major groups according to the olfactory function: normal sense of smell (normosmia) nIHH, and reduced sense of smell (hyposmia/anosmia) Kallmann syndrome (KS). Although mutations in more than 50 genes have been associated with IHH so far, only half of those cases were explained by gene mutations. Various combinations of deleterious variants in different genes as causes of IHH have been increasingly recognized (Oligogenic etiology). In addition to the complexity of inheritance patterns, the spontaneous or sex steroid-induced clinical recovery from IHH, which is seen in approximately 10–20% of cases, blurs further the phenotype/genotype relationship in IHH, and poses challenging steps in new IHH gene discovery. Beyond helping for clinical diagnostics, identification of the genetic mutations in the pathophysiology of IHH is hoped to shed light on the central governance of the hypothalamo-pituitary-gonadal axis through life stages. This review aims to summarize the genetic etiology of IHH and discuss the clinical and physiological ramifications of the gene mutations.

Response of Sex Steroid Hormone Synthesis Substrates in Serum and Testes of Male Tilapia (Oreochromis niloticus) Exposed to Methomyl and Its Recovery Pattern

The response of synthetic substrates of sex steroid hormones—cholesterol (CHO), pregnenolone (PREG), and progesterone (PROG)—in the serum and testes of male tilapia (Oreochromis niloticus) to the environmental estrogen pesticide methomyl (0.2, 2, 20, and 200 μg·L−1) was evaluated using static-water contact toxicity tests. The results showed that low methomyl concentrations (0.2 and 2 μg·L−1) had no significant effects on the contents of CHO, PREG, and PROG in the serum and testes of male tilapia (p > 0.05). Consequently, the concentration of 2 μg·L−1 could be used as a preliminary reference threshold for the non-effective dose of methomyl in male tilapia. Exposure to high methomyl concentrations (20 and 200 μg·L−1) significantly inhibited the levels of CHO, PREG, and PROG in the serum and testes of male tilapia (p < 0.05) and showed a dose–response relationship. Sex steroid hormone synthesis substrate damage to male tilapia caused by less than 20 μg·L−1 methomyl was reversible, while the damage caused by equal to or greater than 200 μg·L−1 methomyl was irreversible when tilapia were transferred to methomyl-free water for 18 days. Thus, a concentration of 200 μg·L−1 could be used as a reference threshold for irreversible damage caused by methomyl in male tilapia.

The study of sex steroid hormone compound in green algae (Chlorophyta) for female fertility: A literature review

Reproductive organ cell damage due to oxidants can cause problems in female fertility, this situation can be prevented and overcome by consuming antioxidants such as algae. Green algae Chlorophyta also contains a steroid that is thought to be useful for normal reproductive health in women. The purpose of this study was to determine the compounds of sex steroid hormones in green algae which are important for female fertility. The systematic review method was used in this study. Based on the results of studies, it shows that green algae contain sterols which through biochemical mechanisms will form sex steroid hormones in the target organ. These hormones play an important role in the regulation of the female reproductive system and the balance of these hormones is crucial for normal fertility in women. Based on this, women should be able to maintain their reproductive health well by consuming foods that contain lots of vitamins and natural fibers that are good for the body such as green algae. Women must also be able to maintain a healthy lifestyle, change bad lifestyles, and avoid environmental risk factors that can cause infertility.

Characterization of cutaneous sex steroid hormone production through analysis of skin secretions

Importance: Systemic sex steroid hormone aberrations often manifest in skin disease. The sebaceous, apocrine, and eccrine glands all play an important role in the response and production of these hormones in the skin. However, our ability to quantify hormonal secretions at the skin surface is limited. Objective: Our study aims to characterize the hormonal landscape of the skin at different anatomical sites and between the sexes through analysis of skin secretions. Design: In this observational pilot study, we collected skin secretions from twelve male and ten female control subjects using commercially available, Sebutape®, from the antecubital fossa, forehead, back, and axilla. We then developed a method to extract and quantify the amount of sex steroid hormones from these secretions through liquid chromatography tandem mass spectrometry (LC-MS/MS). Setting: Outpatient clinic. Participants: 34 participants were enrolled in the study, with 22 participants meeting criteria. Eligibility criteria included age of 18 to 40 and BMI between 15-35. Exclusion criteria included participants outside the ages of 18 to 40, use of antibiotics in the last 6 months, history of hormonal aberrations or chronic skin disorders, and use of hormone altering medications (except oral contraception). Results: Our study detected anatomical site differences most notably in elevated dehydroepiandrosterone in the axilla and androstenedione in the forehead. Several hormonal differences were also detected between male and females consistent with known systemic hormone differences between the sexes. Conclusions: We developed a method to quantify the hormonal levels in skin secretions using Sebutape®. Our approach found that hormonal composition varies based on sex and anatomical site. Additional studies will need to be completed to determine relevant hormonal shifts in clinical skin conditions.

Interleukins 4 and 13 drive lipid abnormalities in skin cells through regulation of sex steroid hormone synthesis

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by skin dryness, inflammation, and itch. A major hallmark of AD is an elevation of the immune cytokines IL-4 and IL-13. These cytokines lead to skin barrier disruption and lipid abnormalities in AD, yet the underlying mechanisms are unclear. Sebaceous glands are specialized sebum-producing epithelial cells that promote skin barrier function by releasing lipids and antimicrobial proteins to the skin surface. Here, we show that in AD, IL-4 and IL-13 stimulate the expression of 3β-hydroxysteroid dehydrogenase 1 (HSD3B1), a key rate-limiting enzyme in sex steroid hormone synthesis, predominantly expressed by sebaceous glands in human skin. HSD3B1 enhances androgen production in sebocytes, and IL-4 and IL-13 drive lipid abnormalities in human sebocytes and keratinocytes through HSD3B1. Consistent with our findings in cells, HSD3B1 expression is elevated in the skin of AD patients and can be restored by treatment with the IL-4Rα monoclonal antibody, Dupilumab. Androgens are also elevated in a mouse model of AD, though the mechanism in mice remains unclear. Our findings illuminate a connection between type 2 immunity and sex steroid hormone synthesis in the skin and suggest that abnormalities in sex steroid hormone synthesis may underlie the disrupted skin barrier in AD. Furthermore, targeting sex steroid hormone synthesis pathways may be a therapeutic avenue to restoring normal skin barrier function in AD patients.

Does Testosterone Administration Increase Competitiveness, Confidence and Financial Risk-taking in Men?

The sex steroid hormone testosterone regulates male-typical behaviors such as aggression and displays of dominance in non-human animals. According to the Challenge Hypothesis, these effects arise from context-sensitive testosterone increases that facilitate inter-male competitions over resources, status, and mates. A growing literature documents similar effects of testosterone on economic behaviors related to competition and risk-taking in humans, though findings to date have been mixed. Here, we report two randomized double-blind placebo-controlled testosterone administration experiments, whose combined sample (N = 334) is substantially larger than any previous investigation of the topic (N1 = 91, N2 = 243). The studies were designed independently by research groups in Europe and the US, and both investigated testosterone’s effects on men’s willingness to compete, confidence, and risk-taking—dimensions of economic behavior that are theoretically linked to the Challenge Hypothesis, show robust sex differences, and predict important real-life outcomes such as career choice. We find no evidence for effects of testosterone on any of the behavioral tasks studied across the two experiments, with effect point estimates that are small and inconsistent. The studies had 90% statistical power to detect effects that are larger than d = 0.68 and d = 0.42 respectively, and equivalence tests confidently reject effects that are greater than these magnitudes. Our findings cast doubt on the proposition that testosterone is a meaningful causal driver of the stereotypically “masculine” dimensions of economic behavior studied, and suggest that even if true effects existed, detecting them experimentally would be challenging.

Ovarian Accumulation of Nanoemulsions: Impact of Mice Age and Particle Size

Nanotechnology in the field of drug delivery comes with great benefits due to the unique physicochemical properties of newly developed nanocarriers. However, they may come as well with severe toxicological side effects because of unwanted accumulation in organs outside of their targeted site of actions. Several studies showed an unintended accumulation of various nanocarriers in female sex organs, especially in the ovaries. Some led to inflammation, fibrosis, or decreasing follicle numbers. However, none of these studies investigated ovarian accumulation in context to both reproductive aging and particle size. Besides the influences of particle size, the biodistribution profile may be altered as well by reproductive aging because of reduced capacities of the reticuloendothelial system (RES), changes in sex steroid hormone levels as well as altering ovarian stromal blood flow. This systematic investigation of the biodistribution of intravenously (i.v) injected nanoemulsions revealed significant dependencies on the two parameters particle size and age starting from juvenile prepubescent to senescent mice. Using fluorescent in vivo and ex vivo imaging, prepubescent mice showed nearly no accumulation of nanoemulsion in their uteri and ovaries, but high accumulations in the organs of the RES liver and spleen independently of the particle size. In fertile adult mice, the accumulation increased significantly in the ovaries with an increased particle size of the nanoemulsions by nearly doubling the portion of the average radiant efficiency (PARE) to ~10% of the total measured signal of all excised organs. With reproductive aging and hence loss of fertility in senescent mice, the accumulation decreased again to moderate levels, again independently of the particle size. In conclusion, the ovarian accumulation of these nanocarriers depended on both the age plus the particle size during maturity.