Metabolic alterations such as insulin resistance are thought to underlie the endothelial dysfunction and low grade inflammation found in morbid obesity. Twenty-six morbidly obese patients, aged 39.0 +/- 10.0 (mean +/- sd), were evaluated before and 4.2 +/- 0.8 months after bariatric surgery. A marked increment in the insulin sensitivity index (S(I)) and the endothelium-dependent vasodilatory response in a dorsal hand vein was observed after weight loss following bariatric surgery. Circulating levels of E-selectin, P-selectin, plasminogen activator inhibitor-1, and von Willebrand factor, which were higher than those in the control group, decreased significantly after surgery. Plasma vascular cell adhesion molecule-1, angiotensin-converting enzyme, intercellular adhesion molecule-1, thrombomodulin, and plasma and intraplatelet cGMP levels did not change after weight loss. All inflammatory markers were higher in morbidly obese patients. After surgery, C- reactive protein and sialic acid diminished, whereas circulating levels of IL-6, TNF-alpha, and its soluble receptors did not. Positive correlations were found between changes in adiposity and S(I) and changes in C-reactive protein and between changes in sialic acid and changes in endothelial function. In conclusion, a marked improvement in S(I), endothelial function, and low grade inflammation was observed in the weight-losing, morbidly obese patients after bariatric surgery. S(I) and adiposity appear to play roles in obesity-related, low grade inflammation that contribute to the endothelial dysfunction observed in morbid obesity.

There is extensive evidence that serotonin (5-HT) is implicated in the neuroendocrine control regulating the secretion of several anterior pituitary hormones. It has also been reported that the posterior pituitary is necessary for prolactin (PRL) response to 5-HT as well as to suckling, in which 5-HT implication has been demonstrated. As we have previously shown that vasoactive intestinal peptide (VIP) mediates through an autocrine or paracrine action the PRL release induced by insulin-like growth factor I, thyrotropin-releasing hormone (TRH) and dopamine withdrawal, the aim of the present work was to determine whether 5-HT has a direct action on pituitary secretion and to study the possible role of pituitary VIP in this situation. Cells from the anterior pituitary lobe (AP) were cultured either alone or together with cells from the posterior pituitary lobe (PP). As melanotropes from PP express glucocorticoid receptors in vitro, both AP cultures and cocultures of AP/PP cells were incubated in the presence or absence of corticosterone (0.1 µg/ml), thus designing four experimental conditions. Then both AP and mixed cultures were incubated with 5-HT (100 nM) for 20, 45 and 180. The release of PRL, growth hormone (GH), corticotropin (ACTH) and luteinizing hormone (LH) was stimulated by 5-HT, but only in cocultures of AP/PP cells preincubated with corticosterone, whereas follicle-stimulating hormone and thyroid-stimulating hormone release was not modified. As AP cultures did not show any response to 5-HT, both in the presence or absence of corticosterone, and as melanotropes are the main cellular type present in the PP cultures, we studied the response of α-melanocyte-stimulating hormone (αMSH) to 5-HT in PP cells cultured with or without corticosterone. Serotonin did not modify αMSH release either in the absence or the presence of corticosterone. VIP release was also stimulated by 5-HT in the cocultures, and the time response profile was only similar to that of PRL. In order to study whether pituitary VIP is implicated in 5-HT action, cocultures preincubated with corticosterone were incubated in the presence of 5-HT, a VIP-receptor antagonist (VIP-At) or simultaneously with 5-HT plus VIP-At. PRL response to 5-HT was abolished by the simultaneous presence of VIP-At, whereas GH, ACTH and LH response remained unchanged. These data demostrate that: (1) 5-HT stimulates the secretion of PRL, GH, ACTH, LH and VIP acting directly at pituitary level on PP, probably by releasing an unidentified mediator from melanotropes; (2) glucocorticoids make the response of AP cells to 5-HT possible due to the presence of PP cells in the coculture; (3) PRL response to 5-HT is mediated through an autocrine and/or paracrine action of VIP.

The neuropeptide somatostatin (SS) plays a role as a modulator of cognitive functions and as a potential tropic factor in the central nervous system. A reduction in SS levels has been demonstrated in the aging brain and in dementia. In addition, insulin-like growth factor I (IGF-I) acts as a paracrine factor in multiple GH actions and is also found in the cerebral hemispheres, where it exerts neurotropic effects. We used aging rats as an in vivo model of GH deficiency to study the possible participation of exogenous GH in the modulation of the cerebral hemispheric SS and IGF-I. Two sets of experiments were carried out. In the first set, the age-related patterns of GH, IGF-I, and SS in the serum, pituitary, and cerebral hemispheres were established. In the second experimental set, 90-day-old (adult) and 2-yr-old (aging) male rats received recombinant human GH (200 micrograms/ sc-day) or vehicle for 7 consecutive days. The serum levels of rat GH and IGF-I as well as pituitary GH messenger RNA decreased in 2-yr-old rats compared with those in adult rats. After GH treatment, pituitary GH messenger RNA levels decreased markedly in the 90-day-old and 2-yr-old rats. Serum immunoreactive GH decreased in the adult animals, whereas it remained unaffected in the aging ones, whereas serum IGF-I levels were not altered by GH treatment in either group. Immunoreactive levels and messenger RNA of both SS and IGF-I were low in the cerebral hemispheres of aging rats, but were restored to the levels found in adult rats after GH treatment. As treatment did not induce changes in the serum IGF-I levels, these results provide evidence of a stimulatory action of peripherally administered GH on the regulation of SS and IGF-I genes in the aging rat in the central nervous system. These data also show a new target action for GH and could provide a molecular basis for the improvement of some symptoms of GH deficiency that occurs after recombinant human GH treatment.

There has been increasing experimental evidence to suggest that insulin-like growth factor 1 (IGF-I) may be one of the essential regulators in the reproductive system of the rat. IGF-I is synthesized in the hypothalamus and IGF-I immunoreactivity increases during puberty. Consequently we hypothesized that centrally located IGF-I might contribute to the initiation of puberty. Centrally located IGF-I was immunoneutralized to assess this hypothesis. Male Wistar rats, 28 days old, were infused intracerebroventricularly with specific purified IgGs from rabbit IGF-I antiserum (IGF-I-Ab). The intracerebroventricular administration of IGF-I-Ab resulted in a reduction in testicular weight and consequently in delayed pubertal development. There was also a reduction in serum testosterone, pituitary immunoreactive (IR) luteinizing hormone (LH) and serum IR follicle-stimulating hormone (FSH). The accumulation of βLH mRNA was not modified, whereas βFSH mRNA was increased. An increment in the serum growth hormone (GH) levels was also observed. There were no significant alterations in hypothalamic IR growth hormone releasing factor content, although IR somatostatin (SRIH) content was increased by IGF-I-Ab. The body weight gain remained unaltered. As a whole, our study suggests that centrally located IGF-I influences pubertal development, production and release of gonadotropins and supports the finding that endogenous centrally located IGF-I plays a role at the initiation of puberty in the male rat. It also gives support to the physiological role of centrally located IGF-I in the release of GH mediated by hypothalamic SRIH at the initiation of puberty.

There is a general interest to know whether lipoprotein(a) [Lp(a)] is under hormonal control. Hypothyroidism is a well known cause of secondary hyperlipidemia, which mainly affects low density lipoprotein (LDL) cholesterol levels, but the result on the effects of L-T4 replacement therapy on the Lp(a) concentration is controversial. We studied 12 severely hypothyroid, hypercholesterolemic patients under basal conditions and during L-T4 treatment. We found a rapid decrease in both LDL cholesterol (5.71 +/- 0.62 vs. 4.37 +/- 0.44 mmol/L basally and after 1 month of thyroid replacement, respectively) and apolipoprotein-B (Apo-B) levels (1.89 +/- 0.02 vs. 1.52 +/- 0.17 g/L, respectively); these changes persisted for up 1 yr of analytical euthyroidism and paralleled the improvement in the thyroid status of the patients. In contrast, the plasma Lp(a) concentration did not change at any time (496 +/- 123, 464 +/- 128, and 441 +/- 110 mg/L under basal conditions and after 1 and 14-15 months of thyroid replacement, respectively), and the small fluctuations observed in some patients did not correlate with those in LDL cholesterol or Apo-B, and were not associated with any particular Apo(a) phenotype. In relation to HDL fractions, high density lipoprotein3 (HDL3) remained stable, but HDL2 cholesterol and phospholipid levels decreased during treatment, changes that were the inverse of those in postheparin plasma hepatic lipase activity. Patients in the present study were normotriglyceridemic, except one who was hypertriglyceridemic at diagnosis, but even in this patient, triglyceride levels were unaffected by T4 substitution therapy, as was postheparin plasma lipoprotein lipase activity. The changes observed in LDL, HDL2, and hepatic lipase activity delineate the lipoprotein-related response to T4 replacement therapy, whereas potential individual fluctuations in Lp(a) levels are probably more dependent on other factors, such as the production rate, which are not affected by thyroid hormones.