The pineal hormone melatonin has attracted great scientific interest since its discovery in 1958. Despite the enormous number of basic and clinical studies the exact role of melatonin in respect to human physiology remains elusive. In humans, two high-affinity receptors for melatonin, MT1 and MT2, belonging to the family of G protein-coupled receptors (GPCRs) have been cloned and identified. The two receptor types activate Gi proteins and MT2 couples additionally to Gq proteins to modulate intracellular events. The individual effects of MT1 and MT2 receptor activation in a variety of cells are complemented by their ability to form homo- and heterodimers, the functional relevance of which is yet to be confirmed. Recently, several melatonin receptor genetic polymorphisms were discovered and implicated in pathology—for instance in type 2 diabetes, autoimmune disease, and cancer. The circadian patterns of melatonin secretion, its pleiotropic effects depending on cell type and condition, and the already demonstrated cross-talks of melatonin receptors with other signal transduction pathways further contribute to the perplexity of research on the role of the pineal hormone in humans. In this review we try to summarize the current knowledge on the membrane melatonin receptor activated cell signaling in physiology and pathology and their relevance to certain disease conditions including cancer.

Background: Unlike in girls, the data on the relationship between pubertal development and body weight in boys are controversial. Methods: We measured the height, body weight, body mass index (BMI), pubic hair stages, testicular volume, penis length and circumference of 4030 boys, aged between 7 and 19 years. According to their body weight, the investigated children and adolescents were divided in four groups at each age: underweight boys (BMI <12th percentile), boys with normal weight (12th–84.99th percentile), overweight boys (85th–94.99th percentile) and boys with obesity (BMI ≥95th percentile), and their data were compared. Results: The onset of puberty occurred when the boys’ weight gained 40.33±9.03 kg (median 39.00) and BMI was 18.62±3.12 kg/m² (median 17.80), whereas the late stage was reached at weight of 62.44±10.39 kg (median 61.00) and BMI 21.47±2.84 kg/m² (median 21.20). Earlier maturing boys were heavier than their coevals, whereas underweight boys developed puberty later. Conclusions: The onset and progression of puberty in boys are in a significant positive relationship with weight and BMI. Moreover, in the overweight boys pubertal development begins and comes to the late stage earlier in comparison with normal weight children, whereas in those who are underweight a delay at every stage of the development is observed.

The neuroendocrine system is known to influence immunity, but the precise interactions between different hormones and autoimmune disorders remain obscure. The present study aimed to investigate the role of daily serum melatonin concentrations in the development of systemic lupus erythematosus (SLE) in women. Case-control study. One-hundred and eleven SLE female patients and 46 healthy women were included in the study. Daily serum melatonin levels were investigated in all participants. SLE patients showed significantly lower daily melatonin levels in comparison to healthy women during the short photoperiod (17.75±7.13 pg/mL [16.05] vs. 21.63±6.60 pg/mL [20.10], p=0.012). Hormone concentrations were inversely related to the SLE activity index (SLEDAI) (r= -0.268, p=0.004), but they did not correlate to any particular American College Rheumatology (ACR) criterion (p>0.05 for all). Daily melatonin levels were decreased in women with systemic lupus erythematosus and correlated inversely to the activity of the autoimmune disease. Further studies are needed to clarify the importance of the pineal and extrapineal melatonin secretion in patients with systemic lupus erythematosus as well as the interrelations between hormones and autoimmunity.

Polycystic ovarian syndrome (PCOS) is a common heterogeneous disorder characterized by multiple clinical features including chronic anovulation, infertility, polycystic ovaries and hyperandrogenic signs. Heredity is an important factor for the development of PCOS, but the search for the specific PCOS related genes is still in progress. Neuroendocrine dysregulation might play a crucial role in the PCOS development, thus the hypothalamic–pituitary secretion as well as gonadotropin receptor changes are important target of research. Two single nucleotide polymorphisms, rs12470652 c.872A>G/p.Asn291Ser and rs2293275 c.935G>A/p.Ser312Asn, in the Luteinizing Hormone/Choriogonadotropin Receptor (LHCGR) gene were studied in healthy Bulgarian women and PCOS patients. The prevalence of both polymorphisms was within the expected ranges for Caucasians and did not differ between the two groups. The heterozygous rs2293275 c.935G>A/p.Ser312Asn PCOS carriers reported infertility more often than both homozygous groups (40% vs. 12.5%, p = 0.022). The same polymorphism was associated with insulin levels in obese PCOS women. The obtained results showed that the rs2293275 c.935G>A/p.Ser312Asn genetic variant could modulate the clinical and hormonal characteristics of PCOS, especially in overweight and obese patients. Thus, larger studies in different ethnic groups and variable PCOS subgroups could reveal important genotype–phenotype associations.