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Leptin, a hormone secreted by the adipose tissue, stimulates anorexigenic peptides and also inhibits orexigenic peptides in hypothalamic arcuate nuclei-located neurons. It also counteracts the starvation-induced suppression of thyroid hormones by up-regulating the expression of preproTRH gene. On the other hand, in addition to its role as a modulator of the thyroid-hypothalamic-hypophysial axis, thyrotropin-releasing hormone (TRH) acts as a modulator of the cardiovascular system. In fact, we reported that overexpression of diencephalic TRH (dTRH) induces hypertension. We have recently shown that, in rats with obesity-induced hypertension, hyperleptinemia may produce an increase of dTRH together with an elevation of arterial blood pressure (ABP) through an increase of sympathetic activity and that these alterations were reversed by antisense oligonucleotide and small interfering RNA against preproTRH treatments. Here we explore the possible role of dTRH as a mediator involved in leptin-induced hypertension in 2 obesity mouse models: agouti-yellow mice, which are hyperleptinemic and hypertensive, and ob/ob mice, which lack functional circulating leptin. These 2 models share some characteristics, but ob/ob mice show lower ABP and plasma catecholamines levels. Then, for the first time, we report that there is a clear association between ABP and dTRH levels in both mouse models, as we have found that dTRH content was elevated in agouti-yellow mice and diminished in ob/ob mice compared with their controls. We also show that, after 3 days of subcutaneous leptin injections (10 microg/12 hours), ABP and dTRH increased significantly in ob/ob mice with no alterations of thyroid hormone levels. These results add evidence to the putative molecular mechanisms for the strong association between obesity and hypertension.

Leptin, an adipocyte-released hormone, modifies food intake and energy expenditure regulating hypothalamic-pituitary-thyroid axis function. We previously reported that thyrotropin-releasing hormone (TRH) precursor gene overexpression induces hypertension in the normal rat and that spontaneously hypertensive rats have central TRH hyperactivity with increased TRH synthesis and release and an elevated TRH receptor number. In both models, intracerebroventricular antisense (AS) treatment against the TRH precursor produced a dose-dependent reduction of the increased diencephalic TRH content while normalizing high arterial blood pressure. In this article, we report that male Wistar rats that were made hypertensive by intracerebroventricular injection of a eucaryotic expression plasmid containing the pre-TRH cDNA showed decreased leptin plasma levels and that pre-TRH AS treatment reversed this phenomenon. In addition, male and female spontaneously hypertensive rats showed lower levels of circulating leptin than did sex-matched Wistar-Kyoto control rats. This difference also was abated by the pre-TRH AS treatment. Conversely, 20 microg ICV leptin induced a long-lasting pressor effect (18 +/- 5 mm Hg, n=6, P<0.01, >60 minutes) that was not observed in pre-TRH AS pretreated rats (2 +/- 3 mm Hg, n=6) but persisted in rats used as controls that were treated with inverted oligonucleotide (20 +/- 6 mm Hg, n=4, P<0.01). These data suggest that in rats with TRH-induced hypertension, leptin is decreased, inducing compensatory adiposity. We propose that because leptin produces central TRH synthesis and release, obesity may induce hypertension through TRH system activation and that the TRH-leptin interaction may thus contribute to the strong association between hypertension and obesity.

The article discusses the results of a study on the association of mitochondrial deoxyribonucleic acid (DNA) content with clinical features, anthropometric variables and laboratory findings in abnormal fetal growth. The association of the mothers' pregestational DNA with the weight of their offspring is explained, and information on the techniques used to measure routine laboratory variables is presented.

Abstract: Thyrotropin (TSH)-releasing hormone (TRH) also known as thyroliberin was the first of a number of peptides exerting several roles as a hormone and as a neuropeptide. Its ubiquitous distribution in the hypothalamus and in the extrahypothalamic regions and its diverse pharmacological and physiological effects are all features of its dual functions. For this reason, TRH has been the subject of much research throughout the past 20 years, work that has examined the structure, function, distribution, and regulation of the tripeptide and it has been extensively reviewed elsewhere [O''Leary R., O''Connor B. Thyrotropin-releasing hormone. J Neurochem. 1995;65:953–963.; Nillni E., Sevarino K. The biology of pro-thyrotropin-releasing hormone-derived peptides. Endocrine Reviews, 1999;20:599–664.]. After a brief overview of its distribution, hypothalamic and extrahypothalamic functions, and receptors involved, this review discusses efforts devoted to support TRH role in cardiovascular regulation with a main focus on hypertension pathophysiology in experimental models and humans. [Copyright &y& Elsevier]