vasoactive-intestinal-peptide and Hyperprolactinemia

We examined a possible GH-releasing activity of vasoactive intestinal peptide (VIP) and its homologous peptide, peptide histidine methionine (PHM), in 22 patients with hyperprolactinemia (HPRL) who comprised 19 cases of prolactinoma (PRLoma) and 3 cases of hypothalamic HPRL. Each patient underwent iv bolus injections of VIP (100 micrograms) and PHM (100 micrograms) on separate days, and plasma levels of GH and PRL were measured. The plasma GH response to VIP and PHM were considered positive (a paradoxical increase) when an increase over baseline of at least 50% occurred. In agreement with previous reports, the PRL-releasing activity of VIP and PHM in our patients with HPRL were subnormal. Thirteen (59%) patients showed a paradoxical rise in GH after VIP, and 4 (18%) patients did so after PHM. It is to be noted that all the 3 patients with hypothalamic HPRL responded to VIP with a significant rise in GH. 3 of the 4 PHM-responders were also responsive to VIP, which suggests that PHM may have activated VIP receptors in the pituitary of the PHM-responders as a partial agonist of the VIP receptor. The responders and nonresponders to VIP or PHM, respectively, had similar results with respect to the mean age, and the mean basal PRL and GH levels in the plasma. Since these paradoxical GH responses were observed in not only the patients with PRLoma but also those with hypothalamic HPRL, it may be that these anomalous GH responses in HPRL were due to the HPRL itself rather than due to the neoplastic lactotrophs.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Female; Growth Hormone; Humans; Hyperprolactinemia; Hypothalamic Diseases; Male; Middle Aged; Peptide PHI; Pituitary Neoplasms; Prolactinoma; Sequence Homology, Amino Acid; Vasoactive Intestinal Peptide

The neuropeptides vasoactive intestinal peptide (VIP) and galanin are synthesized in the anterior pituitary, galanin in the lactotroph and VIP probably in another cell type, and both stimulate prolactin secretion. Oestrogen regulates anterior pituitary VIP and galanin, galanin expression reflecting physiological variation in oestrogen status, whilst VIP is induced by pharmacological concentrations of oestrogen. Implanting anterior pituitaries under the renal capsule to induce hyperprolactinaemia we studied the regulation of anterior pituitary VIP and galanin synthesis and storage by prolactin and its interaction with oestrogen status. Five groups of animals were studied: control, hypophysectomized implanted, implanted, hyperoestrogenized (oestradiol-17 beta; 250 micrograms/day) and hyperoestrogenized implanted. Spontaneously cycling animals were followed through two cycles prior to implanting and were maintained for at least 1 week and then killed once they were in dioestrus. Circulating prolactin levels were significantly elevated in implanted animals but not in hypophysectomized implanted animals compared with controls. There was a more marked increase in prolactin levels in hyperoestrogenized animals and hyperoestrogenized implanted animals, with no significant difference between these two groups. Native anterior pituitary galanin and VIP content was suppressed in implanted animals, and markedly increased in hyperoestrogenized animals. Pituitary implantation only marginally reduced the effect of hyperoestrogenization on galanin content but abolished the effect of hyperoestrogenization on VIP content. Implant peptide content was suppressed to less than 10% of native anterior pituitary content. Galanin was not detected in implants from hypophysectomized-implanted animals but implant VIP content was unaffected by hypophysectomy. VIP content was increased in implants from hyperoestrogenized implanted animals but implant galanin content was unaffected by hyperoestrogenization. Peptide mRNA levels changed in parallel with peptide content except that the implant galanin mRNA levels were increased by hyperoestrogenization. Thus it appears that prolactin negatively regulates anterior pituitary galanin and VIP gene expression and content, probably due to a direct effect on the anterior pituitary and by altered secretion of hypothalamic factors. Oestrogen is a potent stimulus to expression of both peptide genes. Its positive effect on anterior pituitary peptide g

Topics: Animals; Estrogens; Estrus; Feedback; Female; Galanin; Hyperprolactinemia; Hypophysectomy; Pituitary Gland, Anterior; Prolactin; Rats; Rats, Wistar; Vasoactive Intestinal Peptide

Incubation behavior in the turkey hen is associated with a large increase in prolactin secretion. Previous research using hourly sampling of incubating hens has shown that prolactin levels fluctuate widely throughout a 24-hr period, suggestive of pulsatile secretion. This study compared the prolactin secretory patterns of laying and incubating turkeys to determine if prolactin is secreted episodically and if the high prolactin levels characteristic of the incubating hen may result, at least in part, from a change in the amplitude or frequency of secretory pulses. Blood samples were collected from cannulated, unrestrained laying and incubating hens at 10-min intervals for up to 24 hr. Data were analyzed with the PULSAR program to determine baseline prolactin levels and to establish the magnitude, frequency, and duration of episodic secretory peaks. The results revealed tha prolactin is secreted in a pulsatile pattern in both laying and incubating turkey hens. Incubating hens had ninefold higher mean and baseline plasma prolactin levels than laying hens. The prolactin pulses were of approximately 12-fold greater amplitude in incubating hens than in laying hens, but the duration and frequency of pulses were the same in both groups. Therefore, the high prolactin levels required for incubation do not appear to result from an increase in the frequency of lactotroph stimulation, but rather from an increase in the prolactin secretion rate.

Topics: Animals; Female; Hyperprolactinemia; Incidence; Oviposition; Poultry Diseases; Prolactin; Radioimmunoassay; Time Factors; Turkeys; Vasoactive Intestinal Peptide

The median eminence receives fibers from both parvocellular and magnocellular OT neurons in the hypothalamus. The OT neuronal terminal in the median eminence is secretory and is the major source of the neuropeptide in the blood of pituitary portal vessels. The OT secretion into pituitary portal plasma increases by ovarian steroids, PRL, and the suckling stimulus. The OT secretion into the blood of pituitary portal vessels changes in parallel with the altered secretion of PRL from the pituitary. Because of correlative association between pituitary portal plasma OT and systemic plasma PRL and much abundant evidence for a direct stimulatory action of OT on PRL release, we propose that the pituitary portal vascular system serves as the window for the central OT neurotransmission to the pituitary lactotropes.

Topics: Anesthesia; Animals; Estrus; Female; Hyperprolactinemia; Lactation; Liver Circulation; Median Eminence; Oxytocin; Pituitary Gland, Anterior; Prolactin; Rats; Sheep; Vasoactive Intestinal Peptide

Effect of Hachimijiogan (HJ) on dopamine (DA), serotonin (5-HT) and vasoactive intestinal peptide (VIP) was examined in plasma and hypothalamic tissue of sulpiride-induced hyperprolactinemic rats (SHR). Similar to bromocriptine (BR), HJ, in combination with sulpiride, suppressed plasma prolactin levels raised by sulpiride alone. Furthermore, HJ, together with sulpiride, increased plasma DA levels decreased by sulpiride alone, while 5-HT in plasma was increased by sulpiride and HJ, individually or in combination. However, plasma VIP levels were under detection limits on some occasions after HJ treatment. Successively, DA, 5-HT and VIP levels in the hypothalamus were determined. Similar to the effect caused by BR, DA and 5-HT levels in hypothalamic tissue reduced by sulpiride alone were also significantly increased by HJ together with sulpiride, while VIP levels were sometimes under detection levels with or without HJ. These results suggest that HJ stimulates the hypothalamus to increase DA and 5-HT in SHR, providing evidence for the clinical efficiency of HJ in combating hyperprolactinemia. The effect of HJ on VIP in plasma or hypothalamic tissue is, however, questionable.

Topics: Animals; Bromocriptine; Dopamine; Drug Evaluation, Preclinical; Drugs, Chinese Herbal; Female; Hyperprolactinemia; Hypothalamus; Rats; Rats, Inbred Strains; Serotonin; Sulpiride; Vasoactive Intestinal Peptide

Accumulating evidence suggests that vasoactive intestinal peptide (VIP) may be a physiological PRL-releasing factor. In the present study, we examined a possible involvement of VIP in the neonatal androgenization (NA)-induced hyperprolactinemia. Twenty-four hours after birth, newborn female rats were injected sc with 1,000 micrograms of testosterone (NA) or with oil vehicle only (control). Both groups were sacrificed at 8 weeks of age. Compared to controls, NA rats showed significantly higher plasma PRL levels (7.3 fold), anterior pituitary (AP) PRL content (2.1 fold) and plasma estradiol levels (2.1 fold). AP VIP content was extremely higher (61 fold) in NA rats than in controls. However, NA did not affect VIP content in the suprachiasmatic nucleus, paraventricular nucleus or median eminence. These results suggest that the NA-induced hyperprolactinemia may be mediated, at least in part, by paracrine and/or autocrine effects of the increased AP VIP on PRL secretion. However, since the potentiation by NA of the AP VIP content was extremely marked compared to those of the other parameters, the possibility was also raised that the increased AP VIP may be involved in other endocrine and/or nonendocrine events occurring in the AP.

Topics: Androgens; Animals; Animals, Newborn; Estradiol; Female; Hyperprolactinemia; Median Eminence; Paraventricular Hypothalamic Nucleus; Pituitary Gland, Anterior; Prolactin; Radioimmunoassay; Rats; Rats, Inbred Strains; Suprachiasmatic Nucleus; Vasoactive Intestinal Peptide

The effect of the blockade of endogenous VIP by injecting a specific rabbit anti-VIP serum (A-VIP) was studied in rats receiving an acute injection of ethanol. A-VIP administration decreased serum prolactin levels and reduced the hyperprolactinemia induced by ethanol. We also investigated the effect of the acute administration of ethanol on the concentration and release of VIP from the mediobasal hypothalamus. Ethanol decreased VIP concentration in the mediobasal hypothalamus, whereas it stimulated the in vitro K(+)-evoked release of VIP from this tissue. Conversely, ethanol increased VIP concentration in the anterior pituitary gland. The data indicate that VIP may be involved in the pituitary response to ethanol. The increased anterior pituitary VIP after ethanol may be due to an augmented release from the mediobasal hypothalamus.

Topics: Animals; Ethanol; Hyperprolactinemia; Hypothalamus; In Vitro Techniques; Male; Pituitary Gland, Anterior; Prolactin; Rats; Rats, Inbred Strains; Vasoactive Intestinal Peptide

Dopamine has already been recognized as an inhibiting factor of prolactin. On the other hand, the stimulators of prolactin are still judged diversely at the moment. In addition to hypothalamic TRH, serotonine as well as endogenous opiates and VIP are under discussion. The object of our studies was testing the function of VIP in directing prolactin secretion on three different groups of patients: 1. hyperprolactinaemic women of WHO-group VI; 2. patients who had undergone a TRH-test along with an endocrine check-up; 3. post partum in childbed. The determination was made from analyzing peripheral blood by radioimmunoassay. In 20 amenorrhoeic patients of WHO-group VI, their prolactin and VIP levels were determined between 8 and 10 a. m. Only 4 patients showed a VIP-concentration below 20 pg/ml (which represents the limit of detectability). The other 16 patients showed an increased concentration of VIP. In 15 cases there was an obvious correlation of VIP and prolactin concentrations according to the linear regression. In the course of a TRH-test to 20 and 40 minutes after initial blood examination prolactin and VIP were again determined. After 20 minutes all patients showed a threefold increase of the initial prolactin value. On the other hand, VIP increased in 3 cases only. Apart from all those patients who wanted to become pregnant, these three women--being postmenopausal--showed increased initial values already in the unstimulated condition. The third group of patients consisted of 26 women in childbed. Their prolactin and VIP were determined between the second and eight day post partum.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Female; Humans; Hyperprolactinemia; Infertility, Female; Prolactin; Thyrotropin-Releasing Hormone; Vasoactive Intestinal Peptide

The concentration of vasoactive intestinal polypeptide (VIP) in the anterior pituitary gland of female rats was significantly reduced by pituitary implants, prolactin-secreting tumours or dopamine blockade-induced hyperprolactinemia. Oestradiol implants increased plasma prolactin (PRL) to 12 times and increased pituitary VIP to 3.5 times that of controls after one week. The dopamine agonist bromocriptine significantly reduced pituitary VIP at doses within the clinically used range. These results provide evidence for a suppressive effect of plasma PRL on pituitary VIP, which may be effected by a dopaminergic mechanism, but is over-ridden by oestrogen.

Topics: Animals; Bromocriptine; Drug Implants; Estradiol; Female; Fluphenazine; Hyperprolactinemia; Pituitary Gland, Anterior; Prolactin; Rats; Rats, Inbred Strains; Vasoactive Intestinal Peptide

The effect of an iv bolus injection of 1 microgram/kg body weight of vasoactive intestinal polypeptide (VIP) on plasma prolactin (Prl) levels was tested in 13 normal volunteers and 15 patients with hyperprolactinaemia of various aetiology: 9 with Prl-producing pituitary tumours (6 prolactinoma, 3 mixed pituitary adenoma, secreting Prl and growth hormone (GH)), 6 with hyperprolactinaemia secondary to a hypothalamic lesion (4 craniopharyngioma, 1 hypothalamic germinoma, 1 meningoencephalitis). In the normal subjects, an iv injection of VIP caused a prompt increase in plasma Prl with peaks 2- to 3-fold greater than the basal values. On the other hand, none of the 9 patients with a Prl producing pituitary tumour showed any obvious Prl rise after VIP irrespective of a marked difference in their basal Prl levels. Lack of a Prl response to VIP was also found in the 2 patients with hypothalamic lesions (1 craniopharyngioma, 1 hypothalamic germinoma) whose basal Prl concentration was higher than 100 ng/ml. However, in the remaining 4 patients with hypothalamic lesions whose basal Prl concentration was less than 100 ng/ml, VIP injection resulted in a stimulation of the Prl secretion with a maximal net increment of 11.3 +/- 3.8 ng/ml, which is not different statistically form that (16.3 +/- 3.3 ng/ml) in the normal subjects, but significantly higher than that (-2.3 +/- 2.7 ng/ml) in the 4 patients with Prl-secreting adenoma and a basal Prl concentration of less than 100 ng/ml. These results indicate that the VIP test may be a useful diagnostic tool for discriminating a Prl-producing tumour from a hypothalamic lesion in patients with mild hyperprolactinaemia.

Topics: Adenoma; Adolescent; Adult; Child; Diagnosis, Differential; Female; Humans; Hyperprolactinemia; Hypothalamic Diseases; Injections, Intravenous; Male; Middle Aged; Pituitary Neoplasms; Prolactin; Vasoactive Intestinal Peptide