No abstract

Hypergonadotropic ovarian dysgenesis (ODG) with normal karyotype is a heterogeneous condition that in some cases displays Mendelian recessive inheritance. By systematically searching for linkage in multiplex affected families, we mapped a locus for ODG to chromosome 2p. As the previously cloned follicle-stimulating hormone receptor (FSHR) gene had been assigned to 2p, we searched it for mutations. A C566T transition in exon 7 of FSHR predicting an Ala to Val substitution at residue 189 in the extracellular ligand-binding domain segregated perfectly with the disease phenotype. Expression of the gene in transfected cells demonstrated a dramatic reduction of binding capacity and signal transduction, but apparently normal ligand-binding affinity of the mutated receptor. We conclude that the mutation causes ODG in these families.

The new ISA, ISSAM, EAU, EAA and ASA recommendations on the investigation, treatment and monitoring of late-onset hypogonadism in males provide updated evidence-based information for clinicians who diagnose and treat patients with adult onset, age related testosterone deficiency.

Spermatogenesis is a complex developmental process that occurs in several phases. A large number of genes have been identified that are expressed during spermatogenesis, but the biological significance of many of these is not yet known. We have used gene targeting to selectively eliminate the transcription factor CREM (cyclic AMP- responsive element modulator), which is thought to be important for mammalian spermatogenesis. Male mice deficient for all CREM proteins are sterile, as their developing spermatids fail to differentiate into sperm, and postmeiotic gene expression in the testis declines dramatically. The cessation of sperm development is not accompanied by decreases in the levels of follicle-stimulating hormone or testosterone. Our findings indicate that the CREM gene is essential for spermatogenesis, and mice deficient for this transcription factor could serve as a model system for the study of idiopathic infertility in men.

There is no evidence that a uniform structure of testosterone concentrations and complaints exists within the cohort of elderly male patients. Rather, in aging male patients, psychosomatic complaints and metabolic risk relate to testosterone in a symptom-specific manner.