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Steroid Hormone Receptors Involved in Reproduction: Mechanism of Action
Published in Robert E. Garfield, Thomas N. Tabb, Control of Uterine Contractility, 2019
Paul Robel, Baulieu Etienne-Emile
Nonsteroidal antiestrogens were the first hormone antagonists in use. They belong to the triphenyl-ethylene series, and are structurally related to diethylstibestrol, although they bear a third phenolic ring (hence their designation), which is responsible for their antagonistic effects. They are characterized by two complex features: They are pure antagonists in birds, whereas they are strongly estrogenic in mice, the situation being intermediary in the human species;Their agonist properties are dissociated: they stimulate the synthesis of proteins in the liver, for example, the human plasma protein SBP (sex hormone binding protein, which binds estradiol and progesterone), or the uterine and mammary gland progesterone receptor, whereas they generally do not stimulate target cell growth and behave as pure estrogen antagonists in this respect, hence their therapeutic use in estrogen-dependent cancers.
Endocrinology of aging
Published in Philip E. Harris, Pierre-Marc G. Bouloux, Endocrinology in Clinical Practice, 2014
Prasanth N. Surampudi, Christina Wang, Yanhe Lue, Ronald Swerdloff
Testosterone and semen production are primarily dependent on the HPG axis. Gonadal dysfunction results in hormonal dysregulation and changes in cellular function within Leydig cells and Sertoli cells. The hypothalamus synthesizes and secretes gonadotropin-releasing hormone (GnRH) that acts on pituitary gland to produce LH and FSH. LH stimulates Leydig cells to produce testosterone. The decline in testosterone levels can be due to several factors: (1) decreased Leydig cell function, (2) decreased pituitary–hypothalamic axis function with loss of circadian variation, (3) increased levels of sex hormone–binding protein (SHBP) with age, (4) changes in testosterone receptors sensitivity, and (5) effects of altered cardiometabolic and inflammatory markers.78–80
The chemistry of the Body
Published in Gail S. Anderson, Biological Influences on Criminal Behavior, 2019
It has always been understood that the testicles related in some way to sexual ability in males. Farmers knew that a castrated animal could not reproduce, and in days past, the same was seen to be true in humans. So, the testicles, and consequently testosterone, are clearly linked to sperm production and sex drive, but are they related to aggression? It was also common knowledge that castrating, or neutering, an animal reduces its intraspecies aggression and overall “spirit.” A gelded or castrated male horse is much more malleable, and a neutered dog is far less aggressive toward other male dogs. The relationship between aggression and testosterone in animals has been known for decades and has been confirmed in many studies.5 Testosterone plays a major role in sexual behavior, so in animal species it makes evolutionary sense for testosterone to be linked to aggressive behavior, as it will result in acquiring resources and, most importantly, mates. The driving need in all animals is to reproduce and thereby pass their genes on to the next generation, so aggression would help them be “successful.” Studies have shown that levels of testosterone after puberty are highly heritable. A twin study in the Netherlands showed that 66% of the variance was due to genetics in males and 41% in females.6 In another twin and sibling study looking at testosterone and other reproductive hormones—such as inhibin B, follicle-stimulating hormone (FSH), sex hormone-binding protein (SHBP), and luteinizing hormone (LH)—all were found to be highly heritable, with heritability ranging from 56% in testosterone to 81% for SHBP and inhibin B.7 In contrast, in a large study of twin pairs tested at 5 months of age, testosterone levels were determined to be primarily impacted by environment,8 suggesting differences in the mechanisms for prepubertal and postpubertal levels.
Proteomic and bioinformatic analysis of human endometrium from polycystic ovarian syndrome with and without insulin resistance
Published in Gynecological Endocrinology, 2023
Xin Yang, Wang Xiaoping, Ding Nan, Zhang Jian, Li Xiaofeng, Yuan Liwei, Mengni Zhao, Fang Wang
IR is one of the important metabolic signatures of PCOS, appearing in multiple tissues in patients with PCOS, and endometrial IR was previously strongly associated with fertility disorders. Insulin stimulates ovarian theca cells to produce and secrete androgens by reducing the sex hormone binding protein (SHBG) in the liver [4]. IR decreases in nitric oxide (NO) and increases in endothelin-1 (ET-1) in arterial endothelial cells, increases the risk of cardiovascular metabolic diseases. IR increases the likelihood of developing type II diabetes [5]. Insulin also inhibits apoptosis and promotes cell proliferation, inducing endometrial hyperplasia and promoting the growth of endometrial cancer cells, increasing the long-term risk of endometrial cancer in patients with PCOS [6]. However, the mechanism of long-term endometrial cancer in patients with PCOS has not been fully elucidated.
Silexan in anxiety disorders: Clinical data and pharmacological background
Published in The World Journal of Biological Psychiatry, 2018
Siegfried Kasper, Walter E. Müller, Hans-Peter Volz, Hans-Jürgen Möller, Egon Koch, Angelika Dienel
The high prevalence of anxiety and restlessness in younger women (Bekker & van Mens-Verhulst 2007) increases the likelihood of co-administration of contraceptives and anxiolytic drugs. Thus, the interaction potential of Silexan with oral contraceptives was investigated by Heger-Mahn et al. (2014) in a double-blind, randomised cross-over trial testing possible effects of Silexan on the pharmacokinetics and pharmacodynamics of a combination oral contraceptive containing ethinylestradiol (EE) 0.03 mg and levonorgestrel (LNG) 0.15 mg in healthy, fertile, adult females. During two consecutive 28-day cycles, the oral contraceptive was administered for 21 days in combination with Silexan 160 mg/day or placebo. Plasma concentration–time profiles of EE and LNG were obtained on day 18 ± 1. The primary outcome measure was the area under the concentration–time curve over a dosing interval of 24 h (AUCs) for EE and LNG plasma levels. This trial showed that Silexan did not affect the pharmacokinetic properties of the combination oral contraceptive containing EE and LNG to a relevant degree. Similarly, pharmacodynamic parameters such as progesterone, oestradiol, or sex hormone-binding protein levels, mean endometrial thickness, follicle size, and ovarian activity remained unaffected by the administration of Silexan.
Association between serum levels of testosterone and biomarkers of subclinical atherosclerosis
Published in The Aging Male, 2018
Babak Rezanezhad, Rasmus Borgquist, Ronnie Willenheimer, Saad Elzanaty
Several major adverse cardiovascular events were observed in men with low testosterone, suggesting male hypogonadism is a risk factor of cardiometabolic complications [12]. Low testosterone levels were associated with increased risk of aortic atherosclerosis in elderly men [13] independently from age and BMI [14], sex hormone binding protein, total cholesterol, high density lipoprotein, diabetes mellitus, smoking, and alcohol consumption [4]. In the present study, men with low testosterone had significantly higher values of biomarkers of subclinical atherosclerosis compared to those with normal testosterone levels. These findings suggest that hypogonadal men should be informed about the risk of CVD incident, and markers of subclinical atherosclerosis should be considered during hypogonadism workup, particularly in hypogonadal men with family history of CVD.