Evidence and Implications From a Natural Experiment of Prenatal Androgen Effects on Gendered Behavior

Sex and gender are key to people’s lives, and are the focus of scientific and popular interest and controversy. Sex-related psychological characteristics reflect more than socialization; they are influenced by sex hormones present during sensitive periods of development, particularly androgens that are present prenatally. Studies of females with congenital adrenal hyperplasia (CAH) show how prenatal androgens affect behavior across the life span; these hormones have large effects on interest and engagement in gendered activities, moderate effects on spatial abilities, and relatively small (or no) effects on gender identity, gender cognitions, and gendered peer involvement. In addition to showing the complexity of androgens’ effects on gendered behavior, studies of females with CAH provide an opportunity to test theories of gender development, gain insight into how nature and nurture work together, and examine mechanisms of development. The implications of this work have often been misunderstood, so we consider what it means—and does not mean—for biology to influence gender-related behavior.

Prenatal Androgen Effects as a Proximate Mechanism Underpinning Variation in Social Behavior Among Female Nonhuman Primates

While the role of ecological factors in shaping primate social systems has been a central focus for decades, less attention has been given to phylogenetic relationships and the potential role of underlying proximate mechanisms. This study aimed to investigate the relationship between one such proximate mechanism, prenatal androgen effects (PAEs), and aspects of social behavior in female nonhuman primates using the 2D:4D ratio as a proxy for PAEs and phylogenetically controlled methods. In general, female 2D:4D ratios were highest in monogamous species (low inferred PAEs) and lowest in polygynandrous and polygynous species (high inferred PAEs). 2D:4D ratios also varied with the form of polygyny/polygynandry, potentially with regard to the need for competitive over cooperative behaviors and the intensity of female reproductive competition. Species characterized by female dominance had lower 2D:4D ratios than species characterized by male dominance or codominance. There were no significant relationships between 2D:4D ratio and either degree of frugivory or group size. Relationships between 2D:4D ratios and the directional consistency index and 2D:4D ratios and rates of female–female agonism were also nonsignificant although sample sizes for both of these variables were small. Female social relationships are a manifestation of complex competitive and cooperative behaviors and the results suggest that PAEs may act as a proximate mechanism underlying the expression of certain aspects of behavior in female primates in ways that are adaptive to their social system.

OXER1 and RACK1-associated pathway: a promising drug target for breast cancer progression

Recent data indicate that receptor for activated C kinase 1 (RACK1) is a putative prognostic marker and drug target in breast cancer (BC). High RACK1 expression is negatively associated with overall survival, as it seems to promote BC progression. In tumors, RACK1 expression is controlled by a complex balance between glucocorticoids and androgens. Given the fact that androgens and androgenic derivatives can inhibit BC cell proliferation and migration, the role of androgen signaling in regulating RACK1 transcription in mammary tumors is of pivotal interest. Here, we provide evidence that nandrolone (19-nortosterone) inhibits BC cell proliferation and migration by antagonizing the PI3K/Akt/NF-κB signaling pathway, which eventually results in RACK1 downregulation. We also show that nandrolone impairs the PI3K/Akt/NF-κB signaling pathway and decreases RACK1 expression via binding to the membrane-bound receptor, oxoeicosanoid receptor 1 (OXER1). High levels of OXER1 are observed in several BC cell lines and correlate with RACK1 expression and poor prognosis. Our data provide evidence on the role played by the OXER1-dependent intracellular pathway in BC progression and shed light on the mechanisms underlying membrane-dependent androgen effects on RACK1 regulation. Besides the mechanistic relevance, the results of the study are of interest from a translational prospective. In fact, they identify a new and actionable pathway to be used for the design of innovative and rational therapeutic strategies in the context of the personalized treatment of BC. In addition, they draw attention on nandrolone-based compounds that lack hormonal activity as potential anti-tumor agents.

Androgen Effects on the Adrenergic System of the Vascular, Airway, and Cardiac Myocytes and Their Relevance in Pathological Processes

Introduction. Androgen signaling comprises nongenomic and genomic pathways. Nongenomic actions are not related to the binding of the androgen receptor (AR) and occur rapidly. The genomic effects implicate the binding to a cytosolic AR, leading to protein synthesis. Both events are independent of each other. Genomic effects have been associated with different pathologies such as vascular ischemia, hypertension, asthma, and cardiovascular diseases. Catecholamines play a crucial role in regulating vascular smooth muscle (VSM), airway smooth muscle (ASM), and cardiac muscle (CM) function and tone. Objective. The aim of this review is an updated analysis of the role of androgens in the adrenergic system of vascular, airway, and cardiac myocytes. Body. Testosterone (T) favors vasoconstriction, and its concentration fluctuation during life stages can affect the vascular tone and might contribute to the development of hypertension. In the VSM, T increases α1-adrenergic receptors (α1-ARs) and decreases adenylyl cyclase expression, favoring high blood pressure and hypertension. Androgens have also been associated with asthma. During puberty, girls are more susceptible to present asthma symptoms than boys because of the increment in the plasmatic concentrations of T in young men. In the ASM, β2-ARs are responsible for the bronchodilator effect, and T augments the expression of β2-ARs evoking an increase in the relaxing response to salbutamol. The levels of T are also associated with an increment in atherosclerosis and cardiovascular risk. In the CM, activation of α1A-ARs and β2-ARs increases the ionotropic activity, leading to the development of contraction, and T upregulates the expression of both receptors and improves the myocardial performance. Conclusions. Androgens play an essential role in the adrenergic system of vascular, airway, and cardiac myocytes, favoring either a state of health or disease. While the use of androgens as a therapeutic tool for treating asthma symptoms or heart disease is proposed, the vascular system is warmly affected.

The high homeostatic model assessment of insulin resistance as risk factor for acne vulgaris

Background: Acne vulgaris (AV) is a common chronic skin disease involving blockage and or inflammation of pilosebaceous glands which usually affects teenagers and young adults. Elevated sebaceous gland secretion, Propionibacterium acne colonization and inflammation, high androgen effects, and follicular hyperproliferation are the main pathogenic factors of AV. IGF-1 and insulin were studied to stimulate sebaceous lipogenesis. In the skin, besides inducing lipid production in human sebocytes IGF-1 also induces keratinocyte proliferation in vitro and in vivo. HOMA-IR is an examination to determine insulin activity in the basal state.Objective: To prove that high HOMA-IR value is a risk factor for the occurrence of acne vulgaris.Methods: This study is a case control analytic study by comparing HOMA-IR in subjects with AV (case group) and non AV (control group). AV is diagnosed based on clinical predilection. Insulin testing was carried out by the immulite 2000 device through the immunochemiluminescent method.Results: Mean HOMA-IR of case group is 2.63 ± 0.29 meanwhile in the control group was 1.71 ± 0.26 (p <0.001). Subjects with high HOMA-IR had 4.8 times higher risk to experience AV compared to patients with normal HOMA-IR values (p <0.001; 95% IK 2,765-8,332). Conclusion: HOMA-IR values in acne patients were higher than controls. A high HOMA-IR value is an AV risk factor.

Physiological and Pathological Androgen Actions in the Ovary

Androgens, although traditionally thought to be male sex steroids, play important roles in female reproduction, both in healthy and pathological states. This mini-review focuses on recent advances in our knowledge of the role of androgens in the ovary. Androgen receptor (AR) is expressed in oocytes, granulosa cells, and theca cells, and is temporally regulated during follicular development. Mouse knockout studies have shown that AR expression in granulosa cells is critical for normal follicular development and subsequent ovulation. In addition, androgens are involved in regulating dynamic changes in ovarian steroidogenesis that are critical for normal cycling. Androgen effects on follicle development have been incorporated into clinical practice in women with diminished ovarian reserve, albeit with limited success in available literature. At the other extreme, androgen excess leads to disordered follicle development and anovulatory infertility known as polycystic ovary syndrome (PCOS), with studies suggesting that theca cell AR may mediate many of these negative effects. Finally, both prenatal and postnatal animal models of androgen excess have been developed and are being used to study the pathophysiology of PCOS both within the ovary and with regard to overall metabolic health. Taken together, current scientific consensus is that a careful balance of androgen activity in the ovary is necessary for reproductive health in women.