The impact of serotonergic stimulation on reelin and glutamate decarboxylase gene expression in adult female rats.

BACKGROUND: Reelin plays an important role in the regulation of synaptic plasticity in adulthood. Administration of 5-metoxytryptamine (5MT), an agonist of serotonin receptors, during natal and neonatal periods results in decreased reelin expression. In adulthood, reelin is expressed by GABAergic neurons. OBJECTIVES: The purpose of this study was to reveal the effect of elevated serotonergic stimulation on the expression of reelin and glutamate decarboxylase (GAD1) in adulthood as well as on depressive behavior and spatial cognitive abilities in adult female rats. METHODS: Rats were injected with 5MT. A forced swimming test was used for evaluation of the depressive behavior and Morris water maze test was used for evaluation of spatial cognition. Brains were used for measuring the expression of reelin and GAD1. RESULTS: We found a significant decrease in reelin expression in the cerebellum and prefrontal cortex of 5MT-treated rats. GAD1 expression was decreased in the cerebellum of 5MT-treated rats. 5MT-treated rats reached a lower immobility score in the forced swimming test. The Morris water maze test did not reveal any significant differences. CONCLUSION: We have shown that administration of serotonin receptor agonist resulted in a decreased RELN and GAD1 expression in the cerebellum of adult female rats. We propose that this phenomenon might be relevant in the pathogenesis of autism (Fig. 3, Ref. 38). Full Text in free PDF www.bmj.sk.

Testosterone supplementation therapy as a treatment of hypogonadism.

A substantial proportion of older men (ranging from 20% of 60-year-old to 50% of 80-year-old men) have total serum testosterone levels below the normal range for younger men (1). At the age of 75 years, mean plasma testosterone levels are only 65% of levels in young adults, whereas over 25% of these men have bioavailable testosterone levels below the lowest normal limit in young adults. The interindividual variations in the plasma levels are, however, very important and a quarter of men over 75 years old have still testosterone levels within the upper quartile of values in young men (2). Many symptoms associated with aging in men, including muscle atrophy and weakness, osteoporosis, reduced sexual functioning, and increased fat mass, are similar to changes associated with testosterone deficiency in young men. These similarities suggest that testosterone supplementation may prevent or reverse the effects of aging (3), improve the general well being, sexual characteristics and behaviour of elderly men (Fig. 4, Ref. 71).

[Testosterone--effects, metabolism and genetic determination]. / Testosterón--úcinky, metabolizmus a genetická determinácia.

Testosterone (C19H28O2), the main testicular hormone, is 19-carbonic steroid substance with -OH group in position 17. Precursor for its synthesis is cholesterol, or possibly androstendione released by adrenal cortex. Testosterone is produced in smooth endoplasmatic reticulum of Leydig cells of testes. Apart from testes it is also produced in adrenal cortex, liver, kidneys, in fat and muscle tissue, even though in smaller extent--around 5% (Bidlingmaier, F. et al., 1986). Approximately 4-9 mg (13.9-31.2 nmol/l) of testosterone is daily produced in healthy men. Absolute majority, around 99% from overall plasmatic testosterone is bound to albumin, erythrocytes, but mainly to sex hormone binding globulin (SHBG) (Diver, M.J. et al., 2003). Only small proportion (1-2%) of testosterone circulates as free fraction (Ostatníková, D., 2003). Production and secretion of the main androgen in testes is regulated by well known and accepted axis of hypothalamus, hypophysis and testes. Testosterone and its metabolite dihydrotestosterone can influence the expression of genes, development of masculine type of habitus and behavior, acting via androgen receptor (AR) (Zitzmann, M. and Nieschlag, E., 2003). Testosterone can affect also via its metabolites, whose production is conditioned by enzymes. In peripheral tissues is testosterone converted via aromatase to estradiol and via 5alpha-reductase to dihydrotestosterone (Weber, K.S. et al., 1999).