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Traditionally, testosterone and estrogen have been considered to be male and female sex hormones, respectively. However, estradiol, the predominant form of estrogen, also plays a critical role in male sexual function. Estradiol in men is essential for modulating libido, erectile function, and spermatogenesis. Estrogen receptors, as well as aromatase, the enzyme that converts testosterone to estrogen, are abundant in brain, penis, and testis, organs important for sexual function. In the brain, estradiol synthesis is increased in areas related to sexual arousal. In addition, in the penis, estrogen receptors are found throughout the corpus cavernosum with high concentration around neurovascular bundles. Low testosterone and elevated estrogen increase the incidence of erectile dysfunction independently of one another. In the testes, spermatogenesis is modulated at every level by estrogen, starting with the hypothalamus-pituitary-gonadal axis, followed by the Leydig, Sertoli, and germ cells, and finishing with the ductal epithelium, epididymis, and mature sperm. Regulation of testicular cells by estradiol shows both an inhibitory and a stimulatory influence, indicating an intricate symphony of dose-dependent and temporally sensitive modulation. Our goal in this review is to elucidate the overall contribution of estradiol to male sexual function by looking at the hormone＇s effects on erectile function, spermatogenesis, and libido.

Medical management of male infertility has traditionally involved therapies directed toward manipulation of the hypothalamic-pituitary-gonadal axis. The medications available currently are essentially identical to those utilized decades ago. Moreover, these agents require that the infertile patient can produce at least a small number of functional sperm.

Recent increases in the awareness of hypogonadism as a clinical condition have led to more men being managed with testosterone supplementation therapy （TST）. While highly effective at raising serum testosterone levels and controlling the symptoms of hypogonadism such as fatigue and low energy,1 the resultant suppression of the hypothalamic-pituitary-gonadal axis can lead to an inhibition of gonadotropins, including follicle-stimulating hormone （FSH） and luteinizing hormone （LH） and subsequent azoospermia.

Endocrine disrupting chemicals (EDCs) are increasingly viewed as persistent pollutants, similar to natural hormones in function. This paper describes the expression profiles of 7 genes (DMRT, VTG GnRHR FSHR CYP17A CYP19A, and CYP19B) involved in sex steroid synthesis and action as well as sexual development in adult male and female Cynoglossus semilaevis, after exposure to different concentrations of Bisphenol A (BPA) and 17β-estradiol (E2). Both BPA (1, 10, 50, 125, and 250 mg/kg) and E2 (0.5, 5, and 10 mg/kg) induced changes in target gene expression, although the estrogenic effects of E2 as a model estrogen were stronger. Among the 7 genes, VTG CYP17A and CYP19 responded strongly to BPA or E2 exposure and can thus serve as reference biomarkers for estrogenic EDCs exposure in marine teleosts. These data will provide a window to establish a hypothalamic-pituitary-gonadal model in C. semilaevis to better understand the effect pathways of EDCs.

An increasing amount of evidence demonstrates the anti-aging effect of Heshouwu in pill form. In this study, a subacute aging rat model was established by continuous intraperitoneal injection of D-galactose and treated with Heshouwu decoction （a Chinese herb for tonifying the kidney, comprising Heshouwu pill, Herba Epimedii, Radix Salviae Miltiorrhiae, and Poria）. Heshouwu pill treated rats were the positive control group. Radioimmunoassay, immunohistochemical staining, and western blot assay showed hypothalamic gonadotropin-releasing hormone, hypothalamic substance P, and serum gonadotropin levels to be significantly increased in the model rats; the concentrations of hypothalamic ~3-endorphin, and serum levels of insulin-like growth factor I and testosterone were significantly decreased. 1713- and 3[3-hydroxysteroid dehydrogenase expression in testicular tissue was also decreased. Intragastric administration of Heshouwu decoction at high （9.6 g/mL/100 g）, medium （4.8 g/mL/100 g）, and low （2.4 g/mlJ100 g） doses, Heshouwu decoction pretreatment at a medium dose （4.8 g/mL/100 g）, and Heshouwu pill （2.06 g/mL/100 g） significantly reversed these changes. Heshouwu decoction pretreatment and high-dose Heshouwu decoction had the greatest anti-aging effects. These experimental findings indicate that Heshouwu decoction can improve hypothalamic-pituitary-testicular axis secretion in a subacute aging rat model, and prevent and delay gonadal axis aging, with an effect superior to that of Heshouwu pill.