Endocrine Abstracts

It has been hypothesised that the hypothalamo–pituitary gland complex is a prime target through which environmental chemicals may alter reproductive physiology. The aim of this study was to investigate whether exposure to an environmentally relevant mix of chemicals during in utero and post-natal development can alter pituitary function. Pituitary glands were collected from 110 day-old foetuses (8 control and 8 treated) and 18 month old, post-pubertal sheep (8 cont...

Specific ablation of the androgen receptor (AR) in selected target cells prevents the major developmental defects inherent to generalised AR inactivation (Tfm, ARKO) and allows a detailed analysis of the contribution of defined cells and molecular pathways to more complex effects of androgens. We successfully applied this approach in the study of the role of androgens in the control of spermatogenesis, by developing a Cre/loxP-based mouse model with a Sertoli cell (SC)-selecti...

Spermatogenesis is a complex process involving interactions between the somatic cells (Sertoli, Leydig, peritubular) and germ cells within the adult testis. Androgens are key regulators of spermatogenesis and intra-testicular concentrations of testosterone (T), produced by the Leydig cells, are higher than that in blood. Androgen action is mediated by the androgen receptor (AR), an X-chromosome-encoded, ligand-activated, transcription factor. The mechanisms by which androgens ...

The two primary functions of the adult testis (sperm production and hormone production) need to be co-ordinated because sperm production is completely dependent on appropriate hormone (primarily testosterone) production. However, it is equally evident from animal studies that Leydig cell (LC) development and function are also affected by developmental and functional status of the seminiferous tubules. For example, development of the adult LC population is dependent on reduced ...

Smoking by women during pregnancy can result in a 30–48% reduction in sperm count and testis size in the exposed offspring in adulthood, probably because of a decrease in the number of Sertoli cells. Until recently Sertoli cell proliferation was thought to be androgen independent because fetal Sertoli cells do not express the androgen receptor, but new evidence suggests that androgens may play the lead role in regulating Sertoli cell proliferation in fetal (Tan et al.<...

Disorders of male reproductive health, including testicular cancer, cryptorchidism, hypospadias and low sperm counts, are common and may be increasing in incidence. These conditions manifest at different life stages (low sperm counts and testicular cancer in adulthood; cryptorchidism and hypospadias at birth) but are proposed to originate in fetal life. These disorders have therefore been hypothesized to comprise a ‘testicular dysgenesis syndrome’ (TDS), which result...

Background: Lipocalin 2 (NGAL) is considered a pro-inflammatory adipokine. Noting the conflicting reports as to the role of Lipocalin 2 in metabolic disease, it remains unclear whether an acute or chronic state affects its impact on adipocyte function. In an attempt to address this our current studies investigated for the first time in humans, whether Lipocalin 2 in abdominal subcutaneous adipose tissue (AT) may influence mitochondrial function and browning of adipocytes, as c...

Background: In an obese state, pro-inflammatory adipokines can lead to mitochondrial dysfunction and reduced brown adipocytes properties in white adipocytes (BRITE adipocytes), all of which contribute to the pathogenesis of obesity and type 2 diabetes mellitus (T2DM). A recent novel adipokine, asprosin, that influences appetite and glucose homeostasis, appears to drive inflammation in obesity. However, asprosin expression in human adipose tissue (AT) depots, its impact on mito...

Background: Asprosin is a novel adipokine involved in appetite and glucose regulation. During obesity, circulating asprosin is increased, which leads to increased inflammation and can disrupt cellular functions such as mitochondrial respiration. Asthma is a comorbidity of obesity, with both diseases sharing an inflammatory profile and mitochondrial dysfunction. This study investigated the molecular links between asthma and obesity, by exploring whether asprosin causes mitochon...

From human epidemiological and related studies, there is strong (indirect) evidence that common male reproductive disorders that manifest at birth (cryptorchidism, hypospadias) or in adulthood (low sperm count, low testosterone, primary hypogonadism) may have a common origin in foetal life due to impaired androgen (testosterone) production or action; the so-called testicular dysgenesis syndrome (TDS) hypothesis. Whilst the foetal origin of cryptorchidism and hypospadias is sel...