Treatment of benign hyperplasic processes of milk glands in patients with genital endometriosis

Health condition of 137 f emale with genital endometriosis before hormonal therapy and under the influence of antagonists ( danazol) and agonists of gonadotropic hormones (gozerelin, decapeptyl, buserelin) treatment was studied. Frequent association of genital endometriosis and benign breast tumors (91 % ) and e fficiency of using antagonists and agonists of gonadotropins in the occasions of the simultaneous development of hyperplasic processes in the reproductive system were revealed.

Preventive Effect of Anemarrhenae rhizome and Phellodendri cortex on Danazol-Induced in Precocious Puberty in Female Rats and Network Pharmacological Analysis of Active Compounds

Anemarrhenae rhizome and Phellodendri cortex have historically been used for the treatment of precocious puberty (PP) in oriental medicine. Our study aimed to evaluate the effect of APE, a mixture of the extracts from these herbs, against danazol-induced PP in female rats. The offspring were injected danazol to establish the PP model, and then treated with APE daily, and observed for vaginal opening. At the end of the study, the levels of gonadotropic hormones, such as estradiol, follicle-stimulating hormone, and luteinizing hormone, were determined by ELISA. Moreover, the mRNA expression of GnRH, netrin-1, and UNC5C in hypothalamic tissues was determined by real-time PCR. Network pharmacological analysis was performed to predict the active compounds of APE and their potential actions. APE treatment delayed vaginal opening in rats with PP. In addition, APE treatment reduced LH levels and suppressed UNC5C expression. Gene set enrichment analysis revealed that the targets of APE were significantly associated with GnRH signaling and ovarian steroidogenesis pathways. In conclusion, APE may be used as a therapeutic remedy to inhibit the activation of the hypothalamic–pituitary–gonadal axis.

Clinical and molecular genetic features of 3 family cases of the central precocious puberty, due to MKRN3 gene defects

Gonadotropin-dependent precocious puberty (central) is a condition resulting from the early (up to 8 years in girls and 9 years in boys) reactivation of the hypothalamic-pituitary-gonadal axis. An increase in the secretion of sex steroids by the gonads in this form is a consequence of the stimulation of the sex glands by gonadotropic hormones of the pituitary gland. In the absence of central nervous system abnormalities, CPP is classified as idiopathic and as familial in some cases, emphasizing the genetic origin of this disorder. Loss-of-function mutations in Makorin Ring Finger Protein 3 (MKRN3) are the most common identified genetic cause of central precocious puberty compared to sporadic cases. In the present study we performed the first descrition of 3 family cases of central precocious puberty duo to novel MKRN3 gene mutation detected by NGS in the Russian Federation.

Female Factors of Infertility in a Couple

The problem of infertility is relevant to the whole world, that is explaned both by the prevalence (at least 50 million couples on the planet are diagnosed) and by the enormous medical, ecoomic, social and psychological significance. Another important aspect of infertility is the heterogeneity of its causes – about 40% of infertile marriages are caused by the female factor, 35% – male, 20% – a combination of male and female factors and 5% – have no identified factor. In 2019, the American Collegue of Obstetricians and Gynecologists updated the guidelines for the timing and scope of examinations of infertile couples. In particular, if a woman is 35–40 years old, examination and elimination of the probable factor of infertility should be started after 6 months of non-pregnancy, and in the case of age older than 40 years – immediately after the couple’s accost. The expected tactics should not be used if the patient has oligo- or amenorrhea, known uterine and fallopian tube abnormalities, grade III or IV severity of endometriosis, and the couple has known male infertility factors. Ovulation disorders as a factor of infertility include hypothalamic syndrome, polycystic ovary syndrome, premature ovarian failure and hyperprolactinemia, which differ in the content of gonadotropic hormones and ovarian hormones. The adhesion process of the pelvic organs, which restricts the transport of sperm and fertilized egg through the fallopian tubes, is a consequence of endometriosis and inflammatory diseases caused mainly by sexually transmitted pathogens. Endometriosis, in addition to the formation of adhesions in the pelvic cavity, which is characteristic of stage III and IV of the disease, is also a factor in infertility due to elevated concentrations of prostaglandins and proinflammatory cytokines, failed endometrial reciprocity. Among the uterus abnormalities in the violation of fertility are the uterine membrane, leiomyoma with submucosal localization of the node and uterine synechiae. As part of a comprehensive examination of patients with infertility, it is necessary to take into account the study of thyroid function.

Enhancing gonadotrope gene expression through regulatory lncRNAs

The world of long non-coding RNAs (lncRNAs) has opened up massive new prospects in understanding the regulation of gene expression. Not only are there seemingly almost infinite numbers of lncRNAs in the mammalian cell, but they have highly diverse mechanisms of action. In the nucleus, some are chromatin-associated, transcribed from transcriptional enhancers (eRNAs) and/or direct changes in the epigenetic landscape with profound effects on gene expression. The pituitary gonadotrope is responsible for activation of reproduction through production and secretion of appropriate levels of the gonadotropic hormones. As such, it exemplifies a cell whose function is defined through changes in developmental and temporal patterns of gene expression, including those that are hormonally-induced. Roles for diverse distal regulatory elements and eRNAs in gonadotrope biology have only just begun to emerge. Here, we will present an overview of the different kinds of lncRNAs that alter gene expression, and what is known about their roles in regulating some of the key gonadotrope genes. We will also review various screens that have detected differentially expressed pituitary lncRNAs associated with changes in reproductive state, and those whose expression is found to play a role in gonadotrope-derived non-functioning pituitary adenomas. We hope to shed light on this exciting new field, emphasize the open questions, and encourage research to illuminate the roles of lncRNAs in various endocrine systems.

Transcriptome of Distinct LH and FSH Cells Reveals Different Regulation Unique to Each Cell Type

From mammals to fish, gametogenesis and sexual maturation are driven by LH and FSH, the two gonadotropic hormones temporally secreted from the pituitary. Teleost fish are an excellent model for addressing the unique regulation and function of each gonadotropin hormone since, unlike mammals; they synthesize and secrete LH and FSH from distinct cells. By performing cell specific transcriptome analysis of double-labelled transgenic Nile tilapia (Oreochromis niloticus) expressing GFP and RFP in LH or FSH cells, respectively, we identified genes specifically enriched in each cell type. Though GnRH is considered the main neuropeptide regulating LH and FSH, we found that each LH and FSH cell express unique GPCR signature that reveals the direct regulation of additional metabolic and homeostatic hormones (like cholecystokinin, somatostatin and glutamate). Moreover, some of those GPCRs were conserved also in gonadotrophs of mammals (like PACAP receptor, Adropin receptor and GABBA receptor). Next, we had exploited the unique behavior of Nile tilapia where a behavioral hierarchy is created between males, to compare the gene expression in the pituitary and brain of dominant (reproducing) males to a subordinate (non-reproducing) males. By combining the two transcriptome sets we had identified novel players in the hypothalamic regulation of the HPG axis, and revealed how brain aromatase (cyp19a1b), that is enriched specifically in LH cells, is the key factor in regulating the activity of LH and FSH cells in dominant reproducing fish. Thereby, unraveling novel mechanisms in the differential regulation of LH and FSH. The research was funded by the Israel Science Foundation (ISF) no. 1540/17.

Effects of oral macimorelin on copeptin and anterior pituitary hormones in healthy volunteers

Purpose The test with the highest diagnostic accuracy for diabetes insipidus is copeptin measurement after hypertonic saline infusion. However, the procedure is cumbersome and unpleasant due to rapid sodium increase. An oral stimulation test would be highly desirable. Macimorelin, an oral ghrelin agonist, is a newly approved diagnostic test for growth hormone (GH) deficiency, but its effects on copeptin/vasopressin are unknown and the effects on other pituitary hormones only scarcely investigated. Methods In this prospective, interventional, proof-of-concept study Copeptin and anterior pituitary hormones were measured in 28 healthy volunteers on two test days at baseline, 30, 45, 60, 90 and 120 min after a single dose of macimorelin (first visit: 0.5 mg/kg, second visit: 0.75 mg/kg). Results Baseline copeptin levels were 5.26 pmol/L [1.57, 6.81] and did not change after macimorelin intake (0.5 mg/kg: maximal median change 0.40 [− 0.49, 0.65] pmol/L, p = 0.442; 0.75 mg/kg: − 0.13 [− 0.45, 0.17] pmol/L, p = 0.442. Median GH levels increased from 3.67 mU/L with a maximal median change of 94.66 [IQR 56.5; 110.96] mU/L, p < 0.001. No effect was seen on cortisol, ACTH, LH and FSH levels. Prolactin (max. median change 100 [2.5; 146.5] mU/L, p = 0.004) and free thyroxine (fT4) (0.5 [0.2; 0.8] pmol/L, p < 0.001) increased, whereas TSH decreased (− 0.18 [− 0.22, − 0.09] mU/L, p < 0.001). Conclusion We confirm an increase of GH upon macimorelin in healthy volunteers. However, macimorelin did not stimulate copeptin and therefore does not provide an oral test alternative for the diagnosis of diabetes insipidus. Additionally, a stimulatory effect was seen for prolactin and fT4, but not for ACTH and gonadotropic hormones. Registration The trial was registered on ClinicalTrials.gov (NCT03844217) on February 18, 2019.

Current view оn protocols of controlled ovarian hyperstimulation in women of reproductive age with different ovarian reserve

Reproductology is one of the most dynamically developing branches of modern medical science. It becomes especially important in the context of changes of recent years in society, the main of which is the postponement of childbirth compared to previous generations. In addition, such an important and multifactorial problem as infertility encourages scientists to find different ways to overcome it, taking into account the number of etiological factors and different initial reproductive potential of each member of the couple. In vitro fertilization (IVF) can comprehensively solve the problem, as the procedure involves the reconstruction of the process of fertilization under the supervision of the specialist, «bypassing» the critical points that are often affected by pathological processes in male or female organism. One of the main parameters that determines the prospects of using of these assisted reproductive technologies and, in fact, the strategy of IVF cycles, is ovarian reserve, which characterizes the functional ability of the ovary to generate a follicle independently / in response to exogenous influences. In recent decades, many methods have been proposed to assess it and to predict the so-called poor, «bad» ovarian response to stimulation. It goes in accordance with the fact that for patients with reduced ovarian reserve, it is advisable to use adapted schemes of controlled ovarian hyperstimulation (COH), which takes into account the main pathophysiological properties of folliculogenesis in this category of women. Numerous studies show different data on the effectiveness of gonadotropic hormones (gonadotropins, HT) of different origin in women with different ovarian reserve. This article highlights modern ideas about controlled ovarian hyperstimulation using gonadotropic hormones of various origins, demonstrates the main clinical aspects of implementation of available markers of reduced ovarian reserve, analyzes data on the effectiveness of administration of gonadotropin of different origin in patients with different ovarian reserve and possible measures to increase the efficiency of IVF cycles in patients with reduced ovarian reserve. Keywords: in vitro fertilization, controlled ovarian hyperstimulation, ovarian reserve, gonadotropins.

The role of photoperiod and melatonin in the control of seasonal reproduction in mammals

<b>Melatonin secreted by pineal cells is a hormone whose biosynthesis is coordinated by neurons of the master clock located in the hypothalamic suprachiasmatic nuclei (SCN), characterized by the generation of a 24-hour rhythm. In many species of mammals, fluctuations in melatonin secretion affect reproductive functions, e.g. by regulating the frequency and amount of pulsatile secretion of hypothalamic and gonadotropic hormones. Seasonal breeding is a common adaptive strategy among mammals, allowing them to reproduce during the periods of the year that are most favourable for the later survival and growth of the offspring. This type of reproduction is characteristic of sheep, with winter reproductive activity, and hamsters, with summer reproductive activity. In these animals, melatonin synthesis is largely regulated by the photoperiod, which indirectly influences the period of reproductive activity or passivity. The aim of this study was to gather available knowledge on melatonin as a key element controlling seasonal reproduction. The paper presents the general shape of the circadian rhythm and the neuroendocrine mechanism regulating animal reproduction depending on the variable photoperiod. The collected results suggest that melatonin, kisspeptins, gonadotropin-releasing hormone (GnRH), sex hormones and thyroid hormones participate in the regulation of seasonal reproduction in mammals. </b>