Normal Reproductive function in male mice lacking pituitary kisspeptin receptor.

The anterior pituitary secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) regulate gonadal development, gametogenesis and the secretion of the gonadal steroid hormones. The gonadotroph is primarily regulated by hypothalamic secretion of gonadotropin-releasing hormone (GnRH) from neurons of the rostral hypothalamus and is mediated by GnRH receptor signaling. Kisspeptin (KISS1)/kisspeptin receptor (KISS1R) signaling in GnRH neurons plays an essential role in reproductive function. As the kisspeptin receptor is present in the pituitary, kisspeptin signaling via the Kiss1r may regulate reproductive function at the level of pituitary. Using Cre/Lox technology, we deleted the Kiss1r gene in pituitary gonadotropes (PKiRKO). PKiRKO male and females have normal genital development, puberty onset, and fertility. Females have normal LH, FSH and estradiol while males had significantly increased basal serum FSH levels with no differences in basal serum LH, or testosterone levels. Overall, these findings indicate that the pituitary KISS1R does not play a role in male reproduction.

Sex Differences Are Here to Stay: Relevance to Prenatal Care

Sex differences exist in the incidence and presentation of many pregnancy complications, including but not limited to pregnancy loss, spontaneous preterm birth, and fetal growth restriction. Sex differences arise very early in development due to differential gene expression from the X and Y chromosomes, and later may also be influenced by the action of gonadal steroid hormones. Though offspring sex is not considered in most prenatal diagnostic or therapeutic strategies currently in use, it may be beneficial to consider sex differences and the associated mechanisms underlying pregnancy complications. This review will cover (i) the prevalence and presentation of sex differences that occur in perinatal complications, particularly with a focus on the placenta; (ii) possible mechanisms underlying the development of sex differences in placental function and pregnancy phenotypes; and (iii) knowledge gaps that should be addressed in the development of diagnostic or risk prediction tools for such complications, with an emphasis on those for which it would be important to consider sex.

Impact of sex in the prevalence and progression of glioblastomas: the role of gonadal steroid hormones

Background As in other types of cancers, sex is an essential factor in the origin and progression of glioblastomas. Research in the field of endocrinology and cancer suggests that gonadal steroid hormones play an important role in the progression and prevalence of glioblastomas. In the present review, we aim to discuss the actions and mechanism triggered by gonadal steroid hormones in glioblastomas. Main body Glioblastoma is the most common malignant primary brain tumor. According to the epidemiological data, glioblastomas are more frequent in men than in women in a 1.6/1 proportion both in children and adults. This evidence, and the knowledge about sex influence over the prevalence of countless diseases, suggest that male gonadal steroid hormones, such as testosterone, promote glioblastomas growth. In contrast, a protective role of female gonadal steroid hormones (estradiol and progesterone) against glioblastomas has been questioned. Several pieces of evidence demonstrate a variety of effects induced by female and male gonadal steroid hormones in glioblastomas. Several studies indicate that pregnancy, a physiological state with the highest progesterone and estradiol levels, accelerates the progression of low-grade astrocytomas to glioblastomas and increases the symptoms associated with these tumors. In vitro studies have demonstrated that progesterone has a dual role in glioblastoma cells: physiological concentrations promote cell proliferation, migration, and invasion while very high doses (out physiological range) reduce cell proliferation and increases cell death. Conclusion Gonadal steroid hormones can stimulate the progression of glioblastomas through the increase in proliferation, migration, and invasion. However, the effects mentioned above depend on the concentrations of these hormones and the receptor involved in hormone actions. Estradiol and progesterone can exert promoter or protective effects while the role of testosterone has been always associated to glioblastomas progression.

Role of Sex Hormones in Human Body

Gonadal Steroids hormones play an important role in the reproductive and non-reproductive system. Estrogen has important rule in cardiovascular system as it has vasodilator effect and reduces or prevents platelet activation. In addition, it improves the profile of circulating lipoproteins. All of which may explain why women at premenopausal are less likely to have heart disease than menopause women or men. E2 play grate effect on the skeletal system as it is one of the strongest regulators of osteoblast and osteoclast function, and its responsible for the reduction of adipose tissue and regulation of the body weight, and also has dermatological effect,hence it stimulates the proliferation of keratinocytes and prevents their apoptosis, in addition to the progesterone which increases collagen synthesis. Estrogen is necessary for the functioning and integrity of the tissues of the urinary system specially of the lower urinary tract. Sex steroid are crucial for nervous system, as progesterone is important for production of neurosteroid, and estrogen is currently used in Parkinson’s and Alzheimer’s disease because of its effects on mental health. The androgens also have a crucial biological effects on neural, muscle, bone, adipose tissue,prostate, cardiovascular, haemopoietic, and the reproductive systems. The gonadal steroid hormones play an important role in immune system and regulating the immune response against different viral or bacterial infection.

Extracellular Thimet Oligopeptidase is Released with Extracellular Vesicles from Human Prostate Cancer Cells

ABSTRACTAndrogen signaling plays a central role in the development of prostate cancer. Androgen hormone synthesis is tightly governed by the hypothalamic–pituitary–gonadal (HPG) axis, including gonadotropin-releasing hormone (GnRH). Thimet oligopeptidase (TOP) is a biologically significant peptidase known to cleave GnRH and potentially regulate its activity. Thus, TOP can play an important role in the HPG axis through regulating the downstream production and release of gonadal steroid hormones, including androgens, which may further affect prostate cancer development. TOP is known to be secreted out to the extracellular space. Here, we report that extracellular TOP can be associated with extracellular vesicles (EVs). Western blot analysis of EVs isolated from PC3 or DU145 prostate cancer cells revealed that TOP protein is, indeed, carried by the EVs. Budding of EVs from stimulated PC3 prostate cancer cells can also be visualized by confocal microscopy. Significantly, the TOP enzyme carried by EVs is enzymatically active. The present study shows that EV-associated TOP is a novel form of this extracellular peptidase that may play a role in the disease progression of prostate cancer cells.