Beneficial changes on plasma apolipoproteins A and B, high density lipoproteins and oxidized low density lipoproteins in obese women after bariatric surgery: comparison between gastric bypass and sleeve gastrectomy.

BACKGROUND: The beneficial effects in lipid profiles after obesity surgery might be associated with the decrease in cardiovascular risk. However, direct comparison between different surgical techniques has not been extensively performed. METHODS: In the present study we compare 20 obese women submitted to laparoscopic Roux en Y gastric bypass (RYGB) with 20 women submitted to sleeve gastrectomy (SG). Twenty control women matched for age and baseline cardiovascular risk were also included. Both patients and controls were followed up for 1 year after surgery or conventional treatment with diet and exercise, respectively. Lipid profiles were measured at baseline, 6 and 12 months later. Carotid intima-media thickness was measured by ultrasonography at baseline and at the end of the study. RESULTS: Women submitted to bariatric surgery showed a decrease in total cholesterol, triglycerides, oxidized-LDL and ApoB, and an increase in HDL and ApoA concentrations that occurred regardless of the surgical procedure. LDL concentrations, however, decreased only after RYGB whereas Lp(a) showed no changes. We did not observe any correlation between the changes in serum lipid concentrations and those in carotid intima-media thickness. CONCLUSIONS: Sleeve gastrectomy and gastric bypass induce a similar beneficial effect on serum lipids in women with high cardiovascular risk 1 year after surgery.

Circulating free testosterone in obese men after bariatric surgery increases in parallel with insulin sensitivity.

BACKGROUND AND AIM: Male hypogonadism has been linked to obesity and diabetes. We aimed to study the association of changes in insulin sensitivity and testosterone levels in severe obese patients submitted to bariatric surgery. SUBJECTS AND METHODS: Prospective intervention study with twenty consecutive patients who underwent bariatric surgery studied before and after significant weight loss. Serum testosterone, SHBG, fasting glucose, and insulin were measured among others. Free testosterone was calculated with the Vermeulen formula and insulin sensitivity with the homeostatic model assessment (HOMA). RESULTS: At baseline, thirteen patients had low total testosterone levels, whereas eight of these patients also had free testosterone levels below the reference range obtained from the control group. After bariatric surgery total testosterone, SHBG, and free testosterone significantly increased and achieved normal values in all evaluated patients. Insulin sensitivity improved in all of them. Multivariate linear regression showed that changes in fasting glucose (ß=-1.868, p=0.001), insulin (ß=-3.782, p=0.001), weight (ß=-0.622, p=0.002), and SHBG (ß=-0.635, p=0.022) were associated with changes in free testosterone (adjusted R2=0.936, F=26.613, p=0.001). When insulin resistance calculated by HOMA was in the model instead of insulin and glucose, it also was associated (ß=-3.488, p=0.008) with free testosterone (adjusted R2=0.821, F=11.111, p=0.005). CONCLUSIONS: Circulating tes tos terone in obese men increases after bariatric surgery in parallel with an improvement in insulin sensitivity.

Serum concentrations of osteocalcin, procollagen type 1 N-terminal propeptide and beta-CrossLaps in obese subjects with varying degrees of glucose tolerance.

AIMS: To evaluate serum levels of osteocalcin (OC), procollagen type 1 N-terminal propeptide (P1PN) and beta-CrossLaps (beta-CTx) in obese subjects and their relationship with glucose metabolism parameters. SUBJECTS: Sixty-four obese patients classified according to their glucose tolerance. DESIGN: Case-control study. MEASUREMENTS: A 75-g oral glucose tolerance test was performed with determinations of glucose and insulin between 0 and 120 min. Serum concentrations of OC, P1PN and beta-CTx were quantified in baseline samples. RESULTS: Patients with type 2 diabetes (T2D, n = 24) exhibited OC serum levels (2·6 ± 1·0 nm) significantly lower than those found in subjects with normal glucose tolerance (NGT, n = 20, 3·9 ± 1·5 nm, P < 0·01). We found no significant differences in P1NP and beta-CTX levels among patients with NGT, prediabetes and T2D. Multiple regression analysis showed that serum OC concentration, but not P1NP or beta-CTx levels, was independently related to 2-h plasma glucose. CONCLUSION: Obese patients with T2D showed significantly reduced levels of OC in comparison with patients with lower degrees of glucose tolerance derangement. Our results also suggest that OC was the only bone marker independently related to the degree of glucose metabolism derangement in these patients.

Role of calcium malabsorption in the development of secondary hyperparathyroidism after biliopancreatic diversion.

Secondary hyperparathyroidism (SH) is a frequent metabolic complication of bariatric surgery. Around 70%of patients who undergo biliopancreatic diversion (BPD) have this complication in the long term. The aim of this study was to evaluate the relative influence of vitamin D deficiency and calcium malabsorption in the development of SH in patients who underwent BPD. We reviewed the mean values of PTH throughout the post-operative follow-up and of related biochemical data (25-hydroxyvitamin D, calcium, magnesium) of 121 patients who underwent BPD at our institute from November 1996 to November 2004 (mean follow-up 66 months). Mean PTH correlated negatively with mean 25-hydroxyvitamin D (r=-0.27, p=0.003) and with urinary calcium(r=-0.19, p=0.047), and positively with age (r=0.22, p=0.018). However, a high mean PTH was found in 48.7% patients with mean 25-hydroxyvitamin D >or=30 ng/ml and in 80.0% patients with mean 25-hydroxyvitamin D between 20 and 30 ng/ml. The mean PTH was normal in 5 patients without calcium supplements at present, and progressively increased in parallel to the calcium dose in the rest of patients, although mean 25-hydroxyvitamin D levels were not related to the calcium dose. Our data suggest that individual differences in active and/or passive calcium absorption determine intractable SH after BPD in around half of the patients who have normal levels of 25-hydroxyvitamin D and in 80% of patients with 25-hydroxyvitamin D levels between 20 and 30 ng/ml after BPD, worsening with age.

[Importance of artificial nutrition in the resolution and etiologic diagnosis of severe chronic diarrhea: a propos of a case]. / Importancia de la nutrición artificial en la resolución y diagnóstico etiológico de diarrea crónica severa: a propósito de un caso.

We present a case of severe chronic diarrhea requiring parenteral nutritional support to both cover the nutritional needs and allow for intestinal rest for later adaptation to enteral nutrition, altogether allowing for the etiologic diagnosis and disease healing.

[Eucaloric substitution of medium chain triglycerides for dietary long chain fatty acids improves body composition and lipid profile in a patient with human immunodeficiency virus lipodystrophy]. / La sustitución eucalórica de triglicéridos de cadena larga por triglicéridos de cadena media mejora la composición corporal y el perfil lipídico en un paciente con lipodistrofia asociada al virus de la inmunodeficiencia humana.

BACKGROUND: Lipodystrophy is a frequent disorder among patients with human immunodeficiency virus (HIV) infection, characterized by a loss of adipose tissue from the extremities, gluteal region and face, with excess fat in the neck and abdominal region. Metabolic abnormalities such as hyperlipidaemia and diabetes mellitus frequently coexist, posing these patients to an increased cardiovascular risk. Drug therapy may improve some of these metabolic disturbances, but to date there are no treatments for lipodystrophy with proven benefit. CASE REPORT: A 42-year-old man with HIV lipodystrophy was started on a standard low caloric diet with <30% of total fat and <10% of saturated fat, together with rosiglitazone 8 mg daily. After five months of treatment, given that lipodystrophic features and dyslipidaemia were still present in our patient, we tried to further improve therapeutic results by eucaloric substitution of medium chain triglycerides for dietary long chain fatty acids. Three months later, a dramatic change in body composition was shown with an increase in lean mass and a decrease in fat mass, together with an improvement in lipid profile. CONCLUSION: Eucaloric substitution of medium chain triglycerides for dietary long chain fatty acids may produce therapeutic benefits in HIV lipodystrophy.

Autoparacrine action of vasoactive intestinal peptide on dopaminergic control of prolactin secretion.

We have previously reported that pituitary vasoactive intestinal peptide (VIP) mediates through autoparacrine mechanisms insulin-like growth factor-I and TRH-stimulated PRL release. In the present study, we have investigated whether VIP might also be implicated in the PRL increase that follows dopamine (DA) withdrawal. The experiments were carried out in defined medium supplemented or not with T3, as in a previous study we had found that PRL release increases under low T3 culture conditions due to mediation by concomittant stimulus of VIP. Anterior pituitary (AP) cells from adult male rats were incubated for 1 h in the presence of DA (10 microM), a VIP-receptor antagonist (VIP-At) (200 nM), or DA plus VIP-At. Then media were removed and the cells were washed with PBS and reincubated under the same conditions but without the addition of DA. In the first incubation, DA inhibited PRL release by 80%, and VIP release by 20% in both T3-free and T3 medium. In the second period of incubation, PRL and VIP release were increased in AP cells previously exposed to DA. These effects were greater when the cells were cultured in T3-free medium than in T3-medium (225% and 150%, respectively for PRL release; and 155 and 135%, respectively for VIP release). PRL response to DA withdrawal was inhibited by the simultaneous presence of VIP-At. This inhibition was again greater when the cells were incubated in medium supplemented with T2. Thus, the stimulus of DA withdrawal was inhibited by 88% in T2-free medium and by 37% in T3-medium. To investigate whether pituitary VIP messenger RNA (mRNA) expression is under dopaminergic control, AP cells were incubated in the presence or absence of bromocriptine (BC) (10 nM) for 2 and 24 h. After 24 h of incubation, BC decreased mRNA levels of PRL and of the two transcripts which VIP expresses in AP. As with DA, BC also inhibited PRL and VIP release both at 2 and 24 h. These data demonstrate that VIP, at least partially, mediates DA withdrawal-induced PRL release through an autoparacrine action. They also suggest that simultaneous inhibition of pituitary VIP mRNA expression and VIP release may be a necessary mechanism for the dopaminergic inhibition of PRL mRNA expression and PRL release.

Autocrine and/or paracrine action of vasoactive intestinal peptide on thyrotropin-releasing hormone induced prolactin release.

Several in vitro studies have demonstrated that vasoactive intestinal peptide (VIP) modulates basal PRL release in normal and hypothyroid anterior pituitary (AP) cells through an autocrine or paracrine action. As thyroid hormone is an important factor in the regulation of pituitary VIP synthesis and secretion, we analyzed the influence of the absence of thyroid hormone on basal PRL release in vitro to study whether the release of PRL induced by TRH might be mediated by a local action of pituitary VIP. When normal AP cells were cultured in a medium supplemented with a near-physiological concentration of free T2 (0.5 nM), basal PRL and VIP release decreased and PRL secretion was not altered by the blockade of VIP action. This finding allowed us to establish the culture conditions in which basal PRL secretion is apparently not under VIP influence. Consequently, we were able to study whether pituitary VIP may be implicated in TRH-induced PRL release. TRH (100 nM) increased PRL and VIP release in a parallel manner and decreased PRL and VIP intracellular content in incubations from 15-180 min. When AP cells wee incubated simultaneously with TRH and a VIP receptor antagonist, TRH-induced PRL release decreased when incubation lasted more than 30 min, whereas the depletion of PRL intracellular content induced by TRH was unchanged. TRH also slightly increased VIP messenger RNA levels at 3 and 24 h, but PRL messenger RNA levels were not modified. These data demonstrate that pituitary VIP participates in in TRH-induced PRL release and that the effect of thyroid hormone on basal pituitary VIP secretion should be borne in mind when studies on its effect, through autocrine and/or paracrine mechanisms, on PRL release stimulated by PRL-releasing factors are conducted.

Induction of vasoactive intestinal peptide gene expression and prolactin secretion by insulin-like growth factor I in rat pituitary cells: evidence for an autoparacrine regulatory system.

The effects of recombinant human insulin-like growth factor I (IGF-I) on both vasoactive intestinal peptide (VIP) and PRL production and gene expression were studied using rat anterior pituitary cell cultures grown in serum-free defined medium. We also examined whether pituitary VIP could be involved in the PRL response to IGF-I and hence in a paracrine regulatory system. Exposure of cultured anterior pituitary cells to IGF-I (2.6 nM) for 3 h caused a significant decrease in both VIP content and media PRL. Treatment with IGF-I (from 0.65-5.2 nM) for 48 h increased VIP production and VIP messenger RNA (mRNA) accumulation, whereas only an increase in media and intracellular PRL content without changes in mRNA was observed. In all these experiments, IGF-I led to a decrease in both GH secretion and expression. Immunoglobulins G purified from VIP antiserum inhibited IGF-I-induced PRL release without affecting intracellular and mRNA levels. The inhibition of both GH secretion and gene expression induced by IGF-I was not blocked by VIP antiserum. In conclusion, these results indicate that IGF-I induces VIP gene expression, and its secretion and also increases PRL secretion. The effect of IGF-I on PRL release is specifically mediated by VIP through a paracrine or autocrine mechanism.

Triiodothyronine regulates somatostatin gene expression in cultured fetal rat cerebrocortical cells.

The effect of triiodothyronine (T3) on somatostatin (SS) mRNA levels in cultured fetal rat cerebrocortical cells was studied. Two different experimental approaches were sought. They differed in the length of time in which cells were deprived of thyroid hormones prior to the addition of exogenous T3. When the cells were not deprived of thyroid hormones, T3 caused a dose-related decrease in SS mRNA content at all doses tested. However, when the cells were deprived of T3 for 24 h, a biphasic effect was observed. These findings suggest that T3 regulates SS gene expression in fetal cultured cerebrocortical cells.

Burden of illness attributable to subclinical hypothyroidism in the Spanish population.

INTRODUCTION: Subclinical hypothyroidism (SH) has been associated recently to cardiovascular diseases. However, the loss of health it entails remains unknown. This study has assessed the burden of illness attributable to SH in Spain. PATIENTS AND METHODS: Based on the Spanish prevalence data found in international studies, a theoretical model was developed to estimate the Disability Adjusted Life Years (DALYs), Years of Life Lost (YLL) and Years Lost due to Disability (YLD) associated with SH. Prevalence of risk factors, coronary mortality risk and coronary event risk associated with SH were obtained from a review of the literature. An analysis was conducted according to the World Health Organization methodology approach for these studies, using official Spanish sources (hospital discharge records, minimum basic data set [MBDS], inpatient mortality records, etc. RESULTS: In Spain, approximately 2,767,124 people have SH, specifically 1,949,820 with levels of TSH between 4.5 and 6.9mIU/l (70.5%), 538,988 with levels between 7 and 9.9mIU/l (19.5%), and 278,317 between 10 and 19.9mIU/l (10%). These subjects suffer approximately 12,608 cardiac events and 1,388 deaths a year attributed to their SH. This represents 30,550 DALYs (13,124 YLL and 17,426 YLD). Between 1.6 and 7.3% of cardiovascular DALYs can be attributed to SH. CONCLUSION: SH is a silent disease which considerably increases the burden of disease. Evaluation of SH, at least in patients belonging to risk groups, could be cost-effective.

[Influence of weight loss in the clinical evolution, metabolic and psychological of the patients with overweight or obesity]. / Influencia de la pérdida de peso en la evolución clínica, metabólica y psicológica de los pacientes con sobrepeso u obesidad.

INTRODUCTION AND OBJECTIVE: The clinical evolution and psychological well-being of patients with overweight or obesity is still a matter of controversy. The aim of this study is to know the impact of the loss of weight on the evolution of the alterations both clinical and metabolic as psychological in patients with overweight or obesity. PATIENTS AND METHOD: We studied a cohort of 192 patients randomly chosen. All of them were characterized clinically and biochemically. Autoadministered questionnaires were used which were already validated in the Spanish population:the General Health Questionnaire (GHQ-28), and bulimia subescale, the Eating Disorder Inventary (EDI). For the statistical analysis using the statistical program SPSS 15.0. Data are expressed as mean (standard deviation). RESULTS: The weight loss was 3.77 (4.85) kilograms, equivalent to a 3.8 (4.86)% of the total weight, the diameter of the waist was reduced by 3.78 (5.89) centimeters, systolic blood pressure was reduced by 3.36 (15.61) mmHg and diastolic in 2.15 (11.26) mmHg. We also found a decreased significantly of glucose levels 7.37(21.23) mg/dl, insulin levels 2.773 (8.749) IU/ml, HOMA-IR index 0.925 (2.728), triglycerides 12.59 (82.95) mg/dl and uric acid 0.172 (1.13) mg/dl. The basal score of the GHQ-28 was pathological in 44,8% of the studied patients, and after six months of treatment, it improved in 20,8% of the patients (p < 0,001). The EDI bulimia subscale score at the beginning of the treatment was 1,02 (SD 1,91), improving after six months of treatment to 0,65 (SD 1,49) p < 0,002. CONCLUSION: The decrease in weight improves not only clinical parameters and biochemical cardiovascular risk and insulin resistance, but also improves the scale score Goldberg, with higher impact on those with worse baseline GHQ-28 scores.

Chylous ascytes secondary to acute pancreatitis: a case report and review of literature.

Chylous ascites is an uncommon finding which is due to the presence of thoracic or intestinal lymph in the abdominal cavity. It is usually caused by a chronic disruption of the lymphatic system. The present report is one of the rare cases in the literature of chylous ascites secondary to idiopathic acute pancreatitis, which showed a complete resolution with a combination of low fat enteral nutrition with MCT and somatostatin analogs.

Taurine and glucose metabolism: a review.

INTRODUCTION: Taurine has probed to be involved in a wide range of biological processes and to provide several different important health benefits. Its effects have been revealed to be exerted mainly through its antioxidant and anti-inflammatory effects, among other mechanisms. OBJECTIVES AND METHODS: The present review is aimed to provide a solid body of evidence regarding the beneficial effects of taurine in the context of diabetes and its complications, with an special focus on the cardiovascular health impairments so frequently associated to this disease, so that data from this updated systematic review of the literature, may constitute a base to back up future clinical and epidemiological studies, on the possibilities of taurine supplementation as a useful tool for both prevention and treatment of diabetes complications. CONCLUSIONS: We consider results from the different experimental, in vitro studies as well as some clinical ones reviewed, to provide sufficient evidence as to constitute a solid base to back up future clinical and epidemiological studies on the usefulness of taurine supplementation both in the prevention and treatment of diabetes and its complications.

Severe ketoacidosis secondary to starvation in a frutarian patient.

The present paper presents the first clinical case of a patient suffering from Frutarianism a new "Eating disorder" and severe Ketoacidosis. The life-style feed strictly only on fruits (not even other vegetables, since plant death is necessary previous consumption).This behavioural alteration frequently leads to starvation and the subsequent Ketoacidosis due to starvation.

Meal replacement with a low-calorie diet formula in weight loss maintenance after weight loss induction with diet alone.

BACKGROUND/OBJECTIVES: Weight loss in obesity can reduce morbidity and mortality and benefits persist as long as weight loss is maintained. Weight maintenance is difficult in the long term and new strategies need to be developed to achieve this goal. We aimed to evaluate the efficacy of substituting a low-calorie diet formula for a meal in a weight loss program during the maintenance phase. METHODS: Randomized paralleled clinical trial including 62 adult patients with at least a 5% weight loss with diet alone for 6 months, randomized to two groups: daily replacement of one meal with a low-calorie diet formula, or dieting alone for another 6 months (weight maintenance phase). RESULTS: Weight maintenance or further weight loss occurred in 83.9% of patients in the intervention group, whereas only in 58.1% in the control group (P=0.025). As a whole, patients in the intervention group lost a further 3.2+/-3.7% of initial weight compared with a 1.3+/-3.6% in the control group (P=0.030). Body fat mass diminished in both groups, with no differences between them (1.6+/-3.5 vs 1.0+/-9.3 kg, respectively, P=0.239), and the same happened with free fat mass (0.9+/-3.3 vs 0.4+/-6.7 kg, respectively, P=0.471). A multivariate logistic regression analysis (R (2)=0.114, P=0.023) retained only the intervention as a predictor of the achievement of weight maintenance with an odds ratio (95% confidence interval) of 3.756 (1.138-12.391). CONCLUSIONS: Substitution of a low-calorie diet formula for a meal is an effective measure for weight loss maintenance compared with dieting alone.

Mechanisms of reduced body growth in the pubertal feminized male rat: unbalanced estrogen and androgen action on the somatotropic axis.

It is well known that the sex difference in body growth at puberty is modulated by a complex interplay between sex steroids and somatotropic axis; however, the exact role played by sex steroids remains a matter of controversy. The aim of this study was to assess the mechanisms by which sex steroids regulate body growth during pubertal development. Flutamide, a non-steroid-blocking androgen receptor, was subcutaneously administered to 30-d-old male Wistar rats for 4 wk. The blockade of the androgen receptor led to a marked elevation in serum testosterone and an increment in serum estradiol. Flutamide administration decreased body weight gain, serum IGF-I levels, hepatic IGF-I mRNA, and GH receptor mRNA content. There were no significant changes in serum GH concentration, pituitary GH reserve, and pituitary GH mRNA content. Flutamide lowered hypothalamic somatostatin mRNA content and augmented hypothalamic immunoreactive somatostatin stores, but did not alter hypothalamic immunoreactive GH-releasing factor stores. Our findings indicate that during pubertal development of the male rat, the imbalance between androgen and estrogen actions determines an abnormal somatic growth, which is at least partly exerted through the peripheral or hepatic modification of the somatotropic axis that occurs under the high or exclusive action of estrogens. Potential implication of coincident sex-specific regulated mode of pulsatile GH secretion cannot be excluded from this random serum GH sample study.

Varying additive effects of bromocriptine with two somatostatin analogs in cultures of GH-secreting adenomas.

In this study, we have investigated the effect of combined treatment using two somatostatin analogs, lanreotide or octreotide, with bromocriptine on GH release in cultures of GH-secreting pituitary tumors. Sixteen acromegalic patients were included in the study. All patients had been treated with lanreotide prior to the surgery. Five patients (31.2 %) reached GH levels below 2.0 microg/l and normal IGF-I levels according to age and sex after lanreotide treatment. A positive correlation was observed between the lanreotide-induced inhibition of GH release in vitro and serum GH decrease after lanreotide treatment (r = 0.52; p = 0.03). Combined treatment significantly inhibited GH release in vitro in 8 of the 16 tumors (50 %). However, only 5 (31.2 %) of the respective patients had been resistant to presurgical treatment with lanreotide. Three of these 5 patients (18.7 %) responded to a BC concentration similar to that achieved with therapeutic doses, and in 2 patients only when a pharmacological dose of BC was used in the combined treatment. The additive effect was observed with the combination of lanreotide and BC in 6 tumors and with octreotide and BC in 3. Only one tumor showed simultaneous response to both types of combination. These results suggest that the additive effect under the combined treatment might be found between 18 and 30 % of patients who are resistant to these drugs, and that different combinations of somatostatin analogs and dopamine agonists should be tested in resistant patients.

Direct action of serotonin on prolactin, growth hormone, corticotropin and luteinizing hormone release in cocultures of anterior and posterior pituitary lobes: autocrine and/or paracrine action of vasoactive intestinal peptide.

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 microg/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 alpha-melanocyte-stimulating hormone (alphaMSH) to 5-HT in PP cells cultured with or without corticosterone. Serotonin did not modify alphaMSH 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.