Management of Osteoporosis in Men: A Narrative Review

Male osteoporosis is a still largely underdiagnosed pathological condition. As a consequence, bone fragility in men remains undertreated mainly due to the low screening frequency and to controversies in the bone mineral density (BMD) testing standards. Up to the 40% of overall osteoporotic fractures affect men, in spite of the fact that women have a significant higher prevalence of osteoporosis. In addition, in males, hip fractures are associated with increased morbidity and mortality as compared to women. Importantly, male fractures occur about 10 years later in life than women, and, therefore, due to the advanced age, men may have more comorbidities and, consequently, their mortality is about twice the rate in women. Gender differences, which begin during puberty, lead to wider bones in males as compared with females. In men, follicle-stimulating hormones, testosterone, estrogens, and sex hormone-binding levels, together with genetic factors, interact in determining the peak of bone mass, BMD maintenance, and lifetime decrease. As compared with women, men are more frequently affected by secondary osteoporosis. Therefore, in all osteoporotic men, a complete clinical history should be collected and a careful physical examination should be done, in order to find clues of a possible underlying diseases and, ultimately, to guide laboratory testing. Currently, the pharmacological therapy of male osteoporosis includes aminobisphosphonates, denosumab, and teriparatide. Hypogonadal patients may be treated with testosterone replacement therapy. Given that the fractures related to mortality are higher in men than in women, treating male subjects with osteoporosis is of the utmost importance in clinical practice, as it may impact on mortality even more than in women.

Seasonal Fluctuations In Luteinizing Hormones (lh), Follicle Stimulating Hormones (FSH) And Testosterone Levels In Male African Giant Rats.

As part of the several efforts to understand the biology of the African Giant rats (AGR) (Cricetomys gambianus), seasonal changes in the gonadotropin and testosterone levels of the adult male African giant rats of about 1 – 1½ years of age in captivity were investigated during wet and dry seasons in the tropics. Male giant rats (n = 10) were kept for 12 months and blood samples were collected monthly (on 15th of each month), during the dry (November – February) and wet (March – June) seasons for Luteinizing hormone (LH), follicle stimulating hormone (FSH) and testosterone assays. The hormones’ levels were evaluated to suggest the best breeding season for giant rat in South-West Nigeria. The result showed that there were significant variation (p<0.001) in LH and FSH levels in the giant rat in the wet season when compared with the dry season. However, testosterone level was significantly lower (p<0.001) in the wet season than in the dry season. The study showed that sexual activities in the male AGR might be higher in the dry season with peak activities in December in the tropics while the gonadotropins prepare the animals for sexual activities in the dry season. Further studies on the seasonal activities of gonadotropins in the female will give more insight into the sexual receptivity and performance in these animals.

Comprehensive Analysis of Purity and Glycosylation Status of Chinese Marketed Recombinant and Urinary FSHs

Background: Urinary or recombinant Follicle-Stimulating Hormones (uFSH and rhFSH) are regularly applied in controlled ovarian stimulation procedure of assisted reproductive technology. Specific activity and purity of these reagents are of great importance since subtle variations in the contents and glycosylation status of FSH may result in differences in clinical efficacy and safety. Objective: The purpose of this study was to comprehensively analyze the FSH contents, glycosylation status and non-specific protein components of the widely used rhFSH Gonal-F and two Chinese marketed FSHs, r-FSH (JSH) and urinary-derived FSH (LSB). Methods: FSH contents, glycosylation status, and other protein contents in these FSH products were assessed with benchtop assays including SDS-PAGE, HPLC and MALDI-MS. Results: HPLC results showed that the purity of the three products was 81.5±0.06% for Gonal-F, 79.6±0.25% for LSB and 76.5±0.36% for JSH, respectively. In addition, MALDI-MS analysis demonstrated that the Gonal-F contained more types of glycosylated isoforms compared to the local rFSHs. The analytical assessment showed that the urinary-derived FSH contained several other protein components. Conclusion: These results suggest that rhFSH Gonal-F is with high purity and potential high activity.

Gonadoliberin – Synthesis, Secretion, Molecular Mechanisms and Targets of Action

Decapeptide gonadoliberin (GnRH) is the most important regulator of the hypothalamic-pituitary-gonadal (HPG) axis that controls the synthesis and secretion of the luteinizing and follicle-stimulating hormones by gonadotrophs in the adenohypophysis. GnRH is produced by the specialized hypothalamic neurons using the site-specific proteolysis of the precursor protein and is secreted into the portal pituitary system, where it binds to the specific receptors. These receptors belong to the family of G protein-coupled receptors, and they are located on the surface of gonadotrophs and mediate the regulatory effects of GnRH on the gonadotropins production. The result of GnRH binding to them is the activation of phospholipase C and the calcium-dependent pathways, the stimulation of different forms of mitogen-activated protein kinases, as well as the activation of the enzyme adenylyl cyclase and the triggering of cAMP-dependent signaling pathways in the gonadotrophs. The gonadotropins, kisspeptin, sex steroid hormones, insulin, melatonin and a number of transcription factors have an important role in the regulation of GnRH1 gene expression, which encodes the GnRH precursor, as well as the synthesis and secretion of GnRH. The functional activity of GnRH-producing neurons depends on their migration to the hypothalamic region at the early stages of ontogenesis, which is controlled by anosmin, ephrins, and lactosamine-rich surface glycoconjugate. Dysregulation of the migration of GnRH-producing neurons and the impaired production and secretion of GnRH, lead to hypogonadotropic hypogonadism and other dysfunctions of the reproductive system. This review is devoted to the current state of the problem of regulating the synthesis and secretion of GnRH, the mechanisms of migration of hypothalamic GnRH-producing neurons at the early stages of brain development, the functional activity of the GnRH-producing neurons in the adult hypothalamus and the molecular mechanisms of GnRH action on the pituitary gonadotrophs. New experimental data are analyzed, which significantly change the current understanding of the functioning of GnRH-producing neurons and the secretion of GnRH, which is very important for the development of effective approaches for correcting the functions of the HPG axis.

Assisted reproductive technologies in cattle reproduction and selection

In vitro technology is one of the most dynamically developing and more and more stable biotechnological methods today accelerating selection, intensifying reproductive and genetic potential of breeding animals, allowing to increase breeding young animals production by one champion cow up to 5–10 calves per year, reduce generation interval and significantly accelerate process of updating and qualitative improvement of livestock. However, obtaining oocytes competent for in vitro development is one of the critical factors determining success of the method and depending on a number of biological and technical factors. This paper presents results of studies on effect of biological factors of direct and indirect impact on efficiency of obtaining oocytes in the system of transvaginal aspiration for the first time conducted in the Republic of Belarus. Yield of excellent and good quality oocytes increased during aspiration during the luteal phase of estrous cycle and remained almost unchanged during aspiration into the follicular phase. Presence of follicles with diameter over 8 mm in the ovaries during aspiration reduced yield of excellent and good quality oocytes averagely by 9.4 percentage points. Removing the dominant follicle 72 hours prior to aspiration allowed increasing the number of aspirated follicles by 41 %, and yield of oocytes – by 22.9 %. Microstimulation of ovaries prior to aspiration by follicle-stimulating hormones FSG-super and Plusset increased efficiency of aspiration in terms of the main indicators by 19.2–45.9 %. Follicular cyst or persistent corpus luteum in one of the ovaries reduced both quantitative and qualitative indicators of aspiration. The data obtained are of practical importance for development of technology for in vitro embryo production in the system of transvaginal aspiration of oocytes which will help to accelerate breeding process and increase efficiency of breeding work in livestock production in general.Acknowledgments. The research was conducted within the two state research programs: “Biotechnology”, subprogram “Development of biological science, biological education and biological industry for 2007–2011 and for the period up to 2020”, “High technologies and equipment for 2016-2020”, subprogram 1 “Innovative biotechnologies–2020”.