The c.1460C>T Polymorphism of MAO-A Is Associated with the Risk of Depression in Postmenopausal Women

Objective. The aim of the study was an evaluation of possible relationships between polymorphisms of serotoninergic system genes and the risk of depression in postmenopausal women. Methods. We studied 332 women admitted to our department because of climacteric symptoms. The study group included 113 women with a diagnosis of depressive disorder according to the Hamilton rating scale for depression; the controls consisted of 219 women without depression. Serum 17β-estradiol concentrations were evaluated using radioimmunoassay, while polymorphisms in serotoninergic system genes: serotonin receptors 2A (HTR2A), 1B (HTR1B), and 2C (HTR2C); tryptophan hydroxylase 1 (TPH1) and 2 (TPH2), and monoamine oxidase A (MAO-A) were evaluated using polymerase chain reaction-restriction. Results. We found that the 1460T allele of MAO-A c.1460C>T (SNP 1137070) appeared with a significantly higher frequency in depressed female patients than in the control group (P = 0.011) and the combined c.1460CT + TT genotypes were associated with a higher risk of depression (P = 0.0198). Patients with the 1460TT genotype had a significantly higher 17β-estradiol concentration than patients with the 1460CT genotype (P = 0.0065) and 1460CC genotype (P = 0.0018). Conclusions. We concluded that depression in postmenopausal women is closely related to the genetic contribution of MAO-A

The gene encoding the ketogenic enzyme HMGCS2 displays a unique expression during gonad development in mice

Disorders/differences of sex development (DSD) cause profound psychological and reproductive consequences for the affected individuals, however, most are still unexplained at the molecular level. Here, we present a novel gene, 3-hydroxy-3-methylglutaryl coenzyme A synthase 2 (HMGCS2), encoding a metabolic enzyme in the liver important for energy production from fatty acids, that shows an unusual expression pattern in developing fetal mouse gonads. Shortly after gonadal sex determination it is up-regulated in the developing testes following a very similar spatial and temporal pattern as the male-determining gene Sry in Sertoli cells before switching to ovarian enriched expression. To test if Hmgcs2 is important for gonad development in mammals, we pursued two lines of investigations. Firstly, we generated Hmgcs2-null mice using CRISPR/Cas9 and found that these mice had gonads that developed normally even on a sensitized background. Secondly, we screened 46,XY DSD patients with gonadal dysgenesis and identified two unrelated patients with a deletion and a deleterious missense variant in HMGCS2 respectively. However, both variants were heterozygous, suggesting that HMGCS2 might not be the causative gene. Analysis of a larger number of patients in the future might shed more light into the possible association of HMGCS2 with human gonadal development.Stefan Bagheri-Fam, Huijun Chen, Sean Wilson, Katie Ayers, James Hughes, Frederique Sloan-Bena, Pierre Calvel, Gorjana Robevska, Beatriz Puisac, Kamila Kusz-Zamelczyk, Stefania Gimelli, Anna Spik, Jadwiga Jaruzelska, Alina Warenik-Szymankiewicz, Sultana Faradz, Serge Nef, Juan Pie, Paul Thomas, Andrew Sinclair, Dagmar Wilhel

Functional hypothalamic amenorrhea: current view on neuroendocrine aberrations

Functional hypothalamic amenorrhea (FHA) is defined as a non-organic and reversible disorder in which the impairment of gonadotropin-releasing hormone (GnRH) pulsatile secretion plays a key role. There are main three types of FHA: stress-related amenorrhea, weight loss-related amenorrhea and exercise-related amenorrhea. The spectrum of GnRH-luteinizing hormone (LH) disturbances in FHA is very broad and includes lower mean frequency of LH pulses, complete absence of LH pulsatility, normal-appearing secretion pattern and higher mean frequency of LH pulses. Precise mechanisms underlying the pathophysiology of FHA are very complex and unclear. Numerous neuropeptides, neurotransmitters and neurosteroids play important roles in the physiological regulation of GnRH pulsatile secretion and there is evidence that different neuropeptides may be involved in the pathophysiology of FHA. Particular attention is paid to such substances as allopregnanolone, neuropeptide Y, corticotropin-releasing hormone, leptin, ghrelin and beta-endorphin. Some studies reveal significant changes in these mentioned substances in patients with FHA. There are also speculations about use some of these substances or their antagonists in the treatment of FHA

Clinical evaluation of patients with weight loss-related amenorrhea: neuropeptide Y and luteinizing hormone pulsatility

AIM: To characterize patients with weight loss-related amenorrhea and controls with respect to the pulsatility of neuropeptide Y (NPY) and luteinizing hormone (LH). SUBJECTS: Nine young women (aged 20.23+/-2.11 years) diagnosed with weight loss-related amenorrhea (body mass index (BMI) 17.52+/-2.43 kg/m2) and five age-matched (age 21.88+/-3.12 years) normally menstruating (every 28-33 days) controls with normal BMI (23.62+/-3.11 kg/m2) (mean value+/-standard deviation). METHODS: Basal hormonal evaluation included serum follicle-stimulating hormone (FSH), LH, estradiol (E2) and NPY. A pulsatility study investigated NPY and LH episodic release. Patients from control the group were studied during the mid-follicular phase (days 6-8) of the menstrual cycle. RESULTS: Patients with weight loss-related amenorrhea had lower FSH, LH and E2 levels than controls (p < 0.01). Basal serum NPY levels were lower in amenorrheic patients than in menstruating women (p < 0.01). The numbers of NPY and LH peaks were higher in patients with weigh loss-related amenorrhea than in controls (p < 0.01 and p < 0.05, respectively). CONCLUSION: Increased NPY pulsatility may have pathophysiological significance in weight loss-related hypothalamic amenorrhea

Clinical evaluation of patients with weight-loss related amenorrhea: neuropeptide Y and luteinizing hormone pulsatility.

.