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Controlling energy homeostasis involves modulating the desire to eat and regulating energy expenditure. The controlling machinery includes a complex interplay of hormones secreted at various peripheral endocrine endpoints, such as the gastrointestinal tract, the adipose tissue, thyroid gland and thyroid hormone-exporting organs, the ovary and the pancreas, and, last but not least, the brain itself. The peripheral hormones that are the focus of the present review (ghrelin, leptin, thyroid hormones, oestrogen and insulin) play integrated regulatory roles in and provide feedback information on the nutritional and energetic status of the body. As peripheral signals, these hormones modulate central pathways in the brain, including the hypothalamus, to influence food intake, energy expenditure and to maintain energy homeostasis. Since the growth of the literature on the role of various hormones in the regulation of energy homeostasis shows a remarkable and dynamic expansion, it is now becoming increasingly difficult to understand the individual and interactive roles of hormonal mechanisms in their true complexity. Therefore, our goal is to review, in the context of general physiology, the roles of the five bestknown peripheral trophic hormones (ghrelin, leptin, thyroid hormones, oestrogen and insulin, respectively) and discuss their interactions in the hypothalamic regulation of food intake.

Oestrogen (E2) and thyroid hormones (THs) are key regulators of cerebellar development. Recent reports implicate a complex mechanism through which E2 and THs influence the expression levels of each other's receptors (ERs and TRs) to precisely mediate developmental signals and modulate signal strength. We examined the modulating effects of E2 and THs on the expression levels of their receptor mRNAs and proteins in cultured cerebellar cells obtained from 7-day-old rat pups. Cerebellar granule cell cultures were treated with either E2, THs or a combination of these hormones, and resulting receptor expression levels were determined by quantitative PCR and Western blot techniques. The results were compared to non-treated controls and to samples obtained from 14-day-old in situ cerebella. Additionally, we determined the glial effects on the regulation of ER-TR expression levels. The results show that (i) ER and TR expression depends on the combined presence of E2 and THs; (ii) glial cells mediate the hormonal regulation of neuronal ER-TR expression and (iii) loss of tissue integrity results in characteristic changes in ER-TR expression levels. These observations suggest that both E2 and THs, in adequate amounts, are required for the precise orchestration of cerebellar development and that alterations in the ratio of E2/THs may influence signalling mechanisms involved in neurodevelopment. Comparison of data from in vitro and in situ samples revealed a shift in receptor expression levels after loss of tissue integrity, suggesting that such adjusting/regenerative mechanisms may function after cerebellar tissue injury as well.

The purpose of the present study was to examine seizure activity during reduced 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP) production. Ovariectomized Long-Evans rats were stereotaxically implanted with bipolar electrodes above the perforant pathway; silastic implants filled with estradiol-17-benzoate (EB) and progesterone were inserted subcutaneously to mimic diestrus. Estrus was then induced in half of these animals by injection of EB (30 microg) and progesterone (2.5 mg), 48 and 4 h, respectively, prior to perforant pathway stimulation. Half of the estrous and diestrous rats also received a 5alpha-reductase inhibitor, finasteride (50 mg/kg), 6 h prior to perforant pathway stimulation. The estrous condition was associated with reduced number and duration of partial seizures, improved performance on a Morris water maze recovery of function test, reduced neuronal loss in the hilar region of the hippocampus, and elevated central and plasma 3alpha,5alpha-THP, compared to estrus+finasteride, diestrus+vehicle and diestrus+finasteride conditions, which did not differ from each another. These data suggest antiseizure effects of estrus may be caused, in part, by the action of 3alpha,5alpha-THP and that the precipitous decline in 3alpha,5alpha-THP may restore seizure threshold to control levels.

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