Endocrine Abstracts

Despite spermatogenesis is among the most finely regulated processes in our body, few genetic tests are currently routinely used in infertile males. These include analysis of karyotype, Yq microdeletions, CFTR and androgen receptor gene mutations, which collectively account for 15–20% of male infertility. Very little is known about the pathogenic mechanism leading to spermatogenesis disruption in many of these patients, especially those carrying Yq microdeletions. Recent ...

Follicle-stimulating hormone (FSH) is a member of the glycoprotein hormone family that plays a pivotal role in ovarian folliculogenesis and spermatogenesis. FSH receptor (FSHR) is, indeed, highly expressed in granulosa and Sertoli cells respectively. However, recent studies have detected FSHR also in extra-gonadal tissues, such as adipose tissue, bone, endometrium, placenta, endothelium, monocytes, and malignant tissues, suggesting, that the activity of this hormone may not be...

Insulin-like factor 3 (INSL3) is a testis-specific, Leydig cell derived hormone, which we recently demonstrated to play a role in bone metabolism. Young men with mutations in the gene for the INSL3 receptor (Relaxin family peptide 2, RXFP2) are at risk of reduced bone mass and osteoporosis. Consistent with the human phenotype, bone analyses of Rxfp2−/− mice showed decreased bone volume, alterations of the trabecular bone, reduced mineralizing surface, bo...

The gene NR5A1, which encodes steroidogenic factor 1 (SF-1), is a pivotal transcriptional regulator of genes involved in adrenal and gonadal function, including several steroidogenic enzymes and key genes necessary for male sex determination and differentiation, testicular descent and reproduction (such as SOX9, AMH, INSL3, and AR). The most severe phenotypes associated with NR5A1 mutations include gonadal dysgenesis, disorders of sex development (DSD) and adrenal insuf...

Background: Male hypogonadism is defined by low circulating testosterone level associated with signs and symptoms of testosterone deficiency. Although the bidirectional link between hypogonadism and cardiovascular disease has been clarified recently, the association between testosterone and chronic heart failure (CHF) is more controversial. Methods: We critically review published studies relating to testosterone, hypogonadism, and CHF and provide practic...

Objective: To investigate whether routine assessment of free testosterone improves the diagnostic accuracy of functional male hypogonadism.Methods: Total and free testosterone (calculated through SHBG assessment) were determined in 372 male patients (median age 44) referring to our department for sexual symptoms symptoms (188 patients) or infertility (184 men). Low total and free testosterone were defined as < 2.31 ng/ml and <63 pg/ml, respective...

Spermatogenic disruption is normally recognized by low sperm count and FSH levels. However, Leydig cell impairment is also frequent in subjects with primary testicular damage, as evidenced for example by reduced INSL3 and 25(OH)-vitamin D levels. The latter is caused by reduced expression of CYP2R1, a major enzyme involved in 25-hydroxylation of cholecalciferol. Furthermore, testosterone (T) production by the Leydig cells might be also impaired in men with primary spermatogeni...

Introduction: Decreased bone mineral density (BMD) in Klinefelter syndrome (KS) is frequent and it has been traditionally related to low testosterone levels. However, low BMD can be observed also in patients with normal testosterone levels and testosterone replacement therapy does not necessarily increase bone mass in these patients. Nothing is known about vitamin D levels and supplementation in KS. In this study we determine vitamin D status and bone mass in KS subjects and c...

Introduction: Klinefelter syndrome (KS) is characterised by the presence of at least one extra X chromosome and represents the most common chromosomal aberration in men. Apart from infertility, the clinical spectrum of KS is variable and often not directly related to hypogonadism, whose expression is also not unpredictable. Several genetic mechanisms may explain the clinical features and variability of the phenotype in KS. In particular, gene-dosage effects and the parental or...

Introduction: Polymorphisms in the gene for FSH receptor (FSHR) and FSH β subunit (FSHB) might modulate FSH levels and represent genetic markers for a pharmacogenetic approach to male infertility treatment. rs6166 (c.2039 A>G, Asn680Ser) and rs1394205 (c.−29 G>A) in FSHR have been better analysed in women, whereas rs10835638 (−211 G>T) in FSHB seems to have a determinant role especially in men. However, studies considering the combined effect of th...