Endocrine Abstracts

Abstract unavailable....

Androgens influence transcription of their target genes through the activation of the androgen receptor (AR). Binding of the AR to DNA motifs in these genes is a critical step in this signal transduction process. The DNA motifs, called androgen response elements (AREs), can be classified in two classes: the classical AREs, which are in vitro also recognized by the other steroid hormone receptors, and the AR-selective AREs, which display selectivity for the AR. For in...

Background and Objective: It is known that androgens decrease and estrogens increase TBG. In female to male transsexuals under testosterone replacement, decrease of TBG has been shown, but also an increased T3/T4 ratio despite stable free T4 and TSH, suggesting increased conversion to T3 by testosterone. We wanted to study the HPT axis in hypogonadal cis-males before and after testosterone replacement.Method: Prospective observational study in adult male...

Global knockout models of the androgen receptor (ARKO) illustrates the many roles androgens and their receptor have in the development of male reproductive organs and the gender differences in many features like the musculoskeletal system. However, neither the global ARKO nor orchidectomy models discriminate between direct and indirect effects of androgens. To determine direct and indirect effects of androgens on muscle, we developed a muscle-specific ARKO (called satARKO for ...

It is well established that sex steroid deficiency induces bone loss, resulting in osteoporosis. Consequently, global androgen receptor knock out (ARKO) mice have trabecular and cortical osteopenia. Bone cell-specific ARKOs however, have a much less pronounced bone phenotype, suggesting that androgens have an influence on processes in other systems or organs which in turn have an impact on bone metabolism. The kidney is a likely candidate, as it plays an important role in calc...

Aims: We have previously shown that orchidectomy (ORX) in adult mice induces hypercalciuria and upregulation of renal Ca2+ and PO43− transporters, but also bone loss already after 2 weeks. Pretreatment with risedronate inhibited bone resorption and hypercalciuria but confirmed the upregulation of renal Ca2+ and PO43− transporters, suggesting bone-independent renal effects of androgens. We hypothesize...

Introduction: 5 Alpha reductase deficiency (5-ARD) is a rare autosomal recessive disorder causing disturbance of sex development. 5 Alpha reductase is an enzyme involved in steroid metabolism, catalyzing testosterone into dihydrotestosterone (DHT), its potent form. 5-ARD therefore results in lower DHT and higher testosterone values. DHT is crucial for the differentiation of the urogenital sinus and genital tubercle into the external genitalia, urethra and prostate, while the v...

The androgen receptor (AR) is a multidomain transcription factor consisting of an aminoterminal domain (NTD), a DNA binding domain (DBD) and a ligand binding domain (LBD). Binding of androgens marks the start of a sequence of intra- and interdomain communications, DNA binding, coregulator recruitment and gene activation. Besides the DBD-mediated dimerization on the DNA, there is a functionally relevant N/C interaction. The contribution of the intra- and intermolecular N/C inte...

Introduction: Pubertal sex steroids are indispensable for peak bone mass acquisition as well as skeletal sexual dimorphism. In males, both androgen receptor (AR) and estrogen receptor alpha (ERα) are required for optimal periosteal cortical bone expansion, while estrogens limit bone size in females. In early puberty, estrogens directly stimulate longitudinal growth via ERα in cartilage, but also indirectly via growth hormone (GH) and insulin-like growth factor I (IGF...

Enzalutamide (Enza) is a second-generation antiandrogen currently used in the clinic for treatment of metastatic prostate cancer. It significantly prolonged survival of men with metastatic castration resistant prostate cancer after chemotherapy by a median of 4.8 months in comparison to the placebo group. However, in a subset of patient’s beneficial effect of Enza cannot be observed, while others who initially respond eventually develop resistance towards the treatment. U...