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.

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.

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.

Genetic and clinical analysis in 10 Spanish patients with multiple endocrine neoplasia type 1.

Multiple endocrine neoplasia type 1 (MEN 1) is characterised by the combination of tumours of the parathyroid, endocrine pancreas and anterior pituitary glands. In 1988 the MEN 1 gene was mapped to chromosome 11q13 and it was cloned in 1997. This gene contains 10 exons and extends across 9 Kb of genomic DNA; it encodes for a product of 610 amino acid named menin whose function is unknown. We have studied 10 unrelated MEN 1 kindreds by a complete sequencing analysis of the entire gene; mutations were identified in nine of them: five deletions, one insertion, two nonsense mutation and a complex alteration consisting of a deletion and an insertion that can be explained by a hairpin loop model. Two of the mutations have been previously described; the other seven were novel, and they were scattered throughout the coding sequence of the gene. As in previous series, no correlation was found between phenotype and genotype.

Use of a long-acting gonadotrophin-releasing hormone analogue in a postmenopausal woman with hyperandrogenism due to a hilus cell tumour.

OBJECTIVE: The aim of this study was to prove the utility of GnRH analogues for the suppression of androgen secretion in a postmenopausal woman with a suspected virilizing ovarian tumour. DESIGN AND METHODS: We present a case of a 72-year-old woman with virilization of recent onset. Hormonal studies revealed a fourfold increase in serum testosterone levels, normal dehydroepiandrosterone sulphate concentrations and high levels of serum 17-hydroxyprogesterone levels. Computed axial tomography scan of the ovaries was normal and the adrenal glands showed a discrete enlargement. The long-acting GnRH analogue, triptorelin, was injected initially (3.75mg i.m.) and serum hormone levels were measured weekly throughout one month. RESULTS: GnRH produced a decrease in serum testosterone levels to normal values, in parallel with the suppression of serum LH and FSH concentrations. The patient was treated for three months with triptorelin and she experienced an amelioration of the hyperandrogenic symptoms. In order to achieve a diagnosis, the patient was submitted to a laparotomy that revealed a small hilus cell tumour in the left ovary. CONCLUSION: GnRH analogues may offer a good therapeutic option in some states of gonadotrophin-dependent hyperandrogenism of ovarian origin.

Biosynthesis of growth hormone-releasing factor by fetal rat cerebrocortical and hypothalamic cells.

The biosynthesis of growth hormone-releasing factor (GRF) by cerebrocortical tissue is controversial. Although several reports have indicated its presence in certain rat cortical areas and in cultured rat hypothalamic cells, no data exist demonstrating its biosynthesis in these areas. In this study, we have investigated the capacity of fetal rat cerebrocortical and hypothalamic cells in culture for synthesizing GRF. Fetal cerebrocortical and hypothalamic cells were exposed to [3H]Arg for 48 h. Medium and cell extracts were processed and [3H]Arg-IR-rGRF was isolated by affinity chromatography and characterized by HPLC. Intracellular [3H]Arg-IR-rGRF from both hypothalamic and cerebrocortical cells exhibited four major peaks, one of them coeluting with synthetic rGRF. In cerebrocortical cultures, newly synthesized and released [3H]Arg-IR-rGRF showed a similar pattern to the cell content. However, in media from hypothalamic cells, higher hydrophobicity molecular forms were absent. The data demonstrated that fetal cerebrocortical and hypothalamic cells in primary culture synthesize GRF with similar posttranslational processing, but with different molecular patterns of secretion.

Endogenous vasoactive intestinal peptide (VIP) regulates somatostatin secretion by cultured fetal rat cerebral cortical and hypothalamic cells.

To determine the possible physiological role of endogenous vasoactive intestinal peptide (VIP) in the control of cerebral somatostatin (SS), we studied the effect of endogenous VIP blockade on immunoreactive SS (IR-SS) accumulation by fetal rat cerebral cortical and hypothalamic cells in culture. Cells were cultured in minimum essential medium (MEM) with 10% fetal calf serum and 10% horse serum. After 7-10 days 'in vitro' media were replaced with MEMs without sera containing anti-VIP immunoglobulins G (IgG) for 1, 3, 6, 24 or 48 h. Controls received the same amount of IgG from normal rabbit serum (NRS). In another group of experiments, cells were incubated with VIP (10(-11) M to 10(-7) M) for 1, 3, 6 or 24 h. Exposure to anti-VIP IgG resulted in a decreased accumulation of IR-SS in both cerebral cortical and hypothalamic cells, whereas the addition of VIP caused a dose-dependent increase in total IR-SS, these effects being evident after 3 h incubation. The stimulatory action VIP on IR-SS was up to 129%, this being decreased to 86% by the addition of anti-VIP to plates containing 10(-7) M VIP. Patterns of IR-SS accumulation throughout prolonged incubation periods were qualitatively similar (in both cerebrocortical and hypothalamic cells) in the presence or absence of anti-VIP IgG. However, in plates containing anti-VIP, the total amount of IR-SS was lower than in the control groups (IgG from NRS). These findings demonstrate that, at this time of brain development, somatostatinergic neurons may be under the physiological regulation of locally produced VIP.

Hypofibrinolysis associated with vasculopathy in non insulin dependent diabetes mellitus.

The pathogenesis of diabetic vasculopathy has been related to modifications in hemostasis and fibrinolysis. 50 non insulin dependent diabetes mellitus patients have been studied. Euglobulin clot lysis time, fibrin plate, tissue plasminogen activator (t-PA) antigen, plasminogen activator inhibitor (PAI) activity, Protein C and S, cholesterol, triglycerides and Hb A1c were determined in blood samples. Diabetic patients showed decreased fibrinolytic activity, as measured by ECLT, with clearly increased PAI levels. Fibrinolytic response to venous occlusion was lower than normal. Vascular complications were associated both with an even higher PAI activity and with a decreased fibrinolytic response to venous occlusion. Elevated PAI activity and decreased fibrinolytic response to stimulus may contribute to vascular disease in diabetes.

Colonic volvulus and ulcerative jejunoileitis due to occult celiac sprue.

Colonic volvulus is a rare complication of celiac disease. A case is reported of a 46-year-old man with a long-standing history of diarrhea and abdominal distention with a diagnosis of irritable bowel syndrome. After an elective inguinal hernia repair, a cecal volvulus and an ulcerative jejunoileitis developed in the patient that required an extensive intestinal resection. Short bowel syndrome developed and was treated with total parenteral and enteral nutrition. The patient had a poor course after reinitiation of oral diet. Subsequently, celiac sprue was diagnosed and the patient improved with a gluten-free diet.

Primary hyperthyroidism and associated hyperparathyroidism in a patient with myotonic dystrophy: Steinert with hyperthyroidism and hyperparathyroidism.

A patient with myotonic dystrophy and associated primary hyperthyroidism and hyperparathyroidism is described; this association has not been reported previously, to the authors' knowledge. The patient also suffered from hypergonadotropic hypogonadism and hyperinsulinism with insulin resistance. The etiology of hyperthyroidism and hyperparathyroidism is not clear. At surgery, a parathyroid adenoma was extirpated, and a subtotal thyroidectomy was performed. Postoperative course was unremarkable, with consistently normal serum calcium levels but persistently elevated serum parathyroid hormone concentrations. The possibility that the patient had a residual hyperparathyroidism could not be eliminated. Thyroid function was normal. After surgery, the patient reported subjective improvement in his muscle strength. The authors conclude that both diseases-- hyperthyroidism and hyperparathyroidism--exert a negative effect on the myotonic dystrophy and that an early recognition of these two diseases is crucial for the favorable evolution of the patient.

[Silent myocardial ischemia during Holter monitoring in patients with diabetes mellitus]. / Isquemia miocárdica silente durante la monitorización con Holter en pacientes con diabetes mellitus.

UNLABELLED: To evaluate the prevalence and characteristics of silent myocardial ischemia in asymptomatic patients with non insulin dependent diabetes mellitus, 50 diabetic patients (24 males, 26 females; mean age +/- SD = 58.3 +/- 6.4 years) with a normal resting electrocardiogram were prospectively studied. The total group underwent 48 hours electrocardiographic Holter monitoring, medical history, physical examination an a test for cardiac autonomic neuropathy. Serum levels of total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides and Hb A1c were determined. An ischemic episode was defined as asymptomatic ST-segment depression greater than or equal to 1 mm, greater than or equal to 1 min. Day-to-day variability was studied. Six hundred and forty one episodes with a total duration of 1,014 minutes of ischemia were recorded in 29 patients (58%). The mean number of episodes in 48 hours per patients was 19.2 +/- 21.9 and the mean time of ischemia over this period was 149 +/- 374 minutes. The average heart rate at the onset of the episodes was 95.2 +/- 8.4 beats per minute. Two hundred and ninety two (45.6%) episodes occurred without heart rate changes and in 349 (54.4%) episodes an increase in heart rate was detected at the onset of the episode. An important day-to-day variability in the number of episodes (73.8 +/- 29.5%) and ischemia duration (76.9 +/- 88.8%) was found. Fifteen patients had no ischemic episodes in either the first or second monitoring day. Silent ischemia was related to higher levels of total cholesterol (p less than 0.05), LDL-cholesterol (p less than 0.05) and Hb A1c (p less than 0.01) and was associated to diabetes complications: retinopathy (p less than 0.001), peripheral vascular disease (p less than 0.01), polyneuropathy (p less than 0.05), nephropathy (p less than 0.05), and impotence (p less than 0.01). Silent ischemia was not associated to abnormal test for cardiac autonomic neuropathy. CONCLUSIONS: prevalence of silent myocardial ischemia during daily activities in asymptomatic diabetic patients is very high (58%). Both an increase in oxygen demand and a decrease in oxygen supply may be involved in its pathophysiology. In diabetic patients silent ischemia is related to the presence of other risk factors for coronary artery disease and to diabetes complications and shows a marked day-to-day variability.

[Update on the role of diet in recurrent nephrolithiasis]. / Actualización del papel de la dieta en la nefrolitiasis recidivante.

The role of nutritional factors in the pathogenesis of recidivating nephrolithiasis is reviewed. The ingestion of liquid calcium and citrates is inversely associated with the risk of developing stones, while the ingestion of proteins, sodium, uric, and oxalates have a direct relationship. One should not restrict the ingestion of calcium in the diet, but rather one should recommended a normal or high ingestion of some 850 mg/day, and rather, one should restrict the ingestion of proteins, oxalate, and sodium, as well as keeping up a diuresis greater than 1500 cc/day.

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.

[Nutrition and mental function in the elderly]. / Nutrición y función mental en el anciano.

A deterioration in cognitive functions is characteristic of the ageing process and is one of the principle causes for disability in old age. It is possible that some of the neuropsychiatric alterations associated with old age may be due to certain subclinical vitamin deficiencies and, as such, may be corrected in some cases with adequate nutrition. This article presents a broad review of the various research efforts published on the subject.