Search

During a systematic study of women with idiopathic galactorrhea, we observed several patients with normal random serum prolactin (PRL) levels and normal menses, but abnormal sellar tomograms characteristic of a pituitary adenoma. To test the hypothesis that these women might have intermittent PRL hypersecretion, we studied PRL secretion by sampling blood every half hour for 24 h in 10 patients and for 17.5 h in another, and compared the findings to those of a group of 5 normal women. The mean 24-h PRL of the 10 patients (16.8 +/- 7.8 ng/ml; mean +/- SD) was not significantly different from that of the normal women (13.6 +/- 3.2 ng/ml), and each patient showed a normal sleep-associated PRL increment. Three individuals exhibited an abnormally elevated 24-h PRL (greater than 20 ng/ml). Increased PRL secretion occurred primarily at night or in the afternoon. Thyrotropin releasing hormone (TRH) administration caused normal or exaggerated PRL responses in all patients tested. High resolution CT scanning of two of the hypersecretors suggested a microadenoma in one case. In another case whose PRL was normal over 17.5 h, transsphenoidal surgery, carried out because of the tomographic findings and the symptom of headaches, demonstrated a 5-mm chromophobe adenoma that did not contain PRL by immunohistochemistry. Postoperatively the galactorrhea persisted. We conclude that most women with galactorrhea, normal PRL, normal menses, and abnormal tomograms have normal PRL secretion. However, a minority of patients with this syndrome do demonstrate intermittent PRL hypersecretion. The etiology of intermittent PRL hypersecretion and its relevance to galactorrhea have not been determined.(ABSTRACT TRUNCATED AT 250 WORDS)

Previous estimates of PRL pharmacokinetics have been made using radioiodinated human PRL (hPRL) infusions or by measuring serum PRL disappearance following prolactinoma resection. The recent purification of hPRL in significant quantities made it possible to measure the clearance and volume of distribution directly. Studies were also carried out to determine absorption and clearance after im injection. In five normal men whose endogenous PRL secretion was suppressed by dopamine, a loading dose of hPRL (70-90 micrograms) followed by a constant infusion (1.39-2.9 ng/min) produced steady state serum PRL levels of 15.2-25.4 ng/mL by 30-60 min. The calculated mean volume of distribution was 7.3 +/- 2.9 (+/- SD) L. The calculated MCR was 71 +/- 19 mL/min X m2, and the calculated production rate was 802 +/- 377 micrograms/24 h X m2. The plasma disappearance half-life following discontinuation of the infusion was 37 +/- 10 min. The PRL infusate consisted primarily (75.6%) of a 22.5 K dalton species, probably PRL monomer, a component eluting at 45K daltons (16.1% of the total radioimmunoreactivity), probably dimer, and a small amount of a larger mol wt species. Serum obtained during dopamine infusion but before hPRL infusion contained 68.1% of the 22.5K, 7.2% of the 45K, and 24.7% of the larger mol wt moieties. During hPRL infusion in two men there was a relative decrease in the proportion of PRL monomer to 55% and 69% and a relative increase in the PRL dimer to 33% and 18%, respectively. hPRL was injected im in doses of 1, 2, 4, and 8 micrograms/kg without prior dopamine infusion. No significant changes in serum PRL levels occurred after the 1 and 2 micrograms/kg doses (n = 5). After the 4 micrograms/kg dose (n = 8), mean serum PRL levels rose from 10.0 +/- 1.8 (+/- SEM) ng/mL to peak levels of 13.1 +/- 1.8 ng/mL (P less than 0.01). After the 8 micrograms/kg dose (n = 7), PRL levels rose from 9.3 +/- 1.6 to 16.5 +/- 1.8 ng/mL (P less than 0.01). The PRL rise began between 60 and 80 min after injection; peak levels occurred at 160-180 min. In two men given 8 micrograms/kg who were sampled for an additional 3 h, PRL levels peaked at 200-220 min and began to fall by 220-240 min, but had not returned to baseline by 6 h. There were no side-effects of PRL administration, although the 8 micrograms/kg dose caused transient local discomfort.(ABSTRACT TRUNCATED AT 400 WORDS)

Twelve hyperprolactinemic women were administered the alpha aminoergoline derivative, CU 32-085 (Sandoz, Inc., East Hanover, NJ), in order to determine its effect on prolactin (PRL) secretion. The mean pretreatment serum PRL level was 145.0 +/- 11.5 ng/ml. Significant declines of serum PRL occurred with total daily doses of CU 32-085 of 0.1 to 0.5 mg (P less than 0.001). The magnitude of response to therapy was dose-related. In six patients, PRL levels were reduced to less than 25 ng/ml; this effect lasted at least 24 hours after intake of a single dose. In the other six patients, the response was less dramatic. No subjects developed adverse cardiovascular side effects. The results of this study demonstrate that CU 32-085 exhibits a clinically significant dopaminomimetic action on PRL secretion in hyperprolactinemic women.

Mazindol, diethylpropion, and a placebo were compared with behavioral therapy for effectiveness in producing weight reduction in an outpatient obesity clinic. Each method was also compared in cost and harmful side effects. The patients were recruited from the middle and lower socioeconomic groups. Of the 120 patients beginning treatment, only 33 completed the entire 14-week study. There was no statistically significant difference in the weight loss among the treatment groups. The program of behavioral therapy was administered by a dietitian who as experienced in the techniques of behavior modification; the drug treatment groups were seen by physicians. We conclude that behavioral therapy may be the treatment of choice in an outpatient obese population since it requires little physician time, is less expensive, and avoids the side effects of anorectic drugs.

This 55-year-old woman presented with primary adrenal insufficiency that led to multiple endocrine gland dysfunctions. Despite symptoms suggestive of hypothyroidism, she had mildly elevated serum thyroid hormone levels associated with elevated thyrotropin levels, hyperprolactinemia, and mild hypercalcemia. These abnormalities corrected with corticosteroid replacement but could be reproduced, in part, when the corticosteroids were temporarily withdrawn. The findings in this patient suggest that physiologic concentrations of glucocorticoids modulate prolactin secretion and the pituitary-thyroid axis. Adrenal insufficiency should be considered in the differential diagnosis of hyperprolactinemia and hyperthyrotropinemia with or without associated hyperthyroxinemia.

We report three patients with craniopharyngiomas who had galactorrhea, oligo/amenorrhea, and abnormal sellar tomograms, clinically suggesting the presence of a prolactinoma. One patient had an intrasellar craniopharyngioma (Rathke's cleft cyst) diagosed during surgical exploration of the pituitary fossa for removal of a suspected prolactinoma, and two had suprasellar caraniopharyngiomas whose presence was suspected on the basis of computed tomography. This finding emphasizes the importance of computed tomography in the evaluation of patients with the clinical presentation of a prolactinoma. In two patients, PRL levels were elevated before surgery and remained elevated after removal of the craniopharyngioma. In the third case, an initially normal serum PRL level became elevated after removal of the tumor.

Thirty women with prolactin (PRL)-secreting adenomas underwent selective adenomectomy via a transsphenoidal route. All had abnormal sella polytomes or visual fields, amenorrhea with low basal serum gonadotropin levels despite decreased serum estradiol concentrations, and elevated basal serum PRL levels with blunted PRL response to neuroendocrine stimulation tests )thyrotropin-releasing hormone, levodopa, chlorpromazine, and hypoglycemia). Of 17 patients with microadenomas, 14 (82.4%) were cured and three (17.6%) improved. None were unchanged or worse. Three (60%) of five patients with larger, but still intrasellar tumors, had normalization of PRL levels, return of menses, and resolution of galactorrhea. The patients with tumors extending out of the sella did not fare as well. Overall, 21 (70%) were cured, six (20%) improved, two (6.7%) were unchanged, and the condition of one (3.3%) became worse. All preoperative neurologic deficits resolved. Postoperative complications were minimal with no neurologic morbidity. When tumors are small, surgical results are excellent with minimal risk.

In a randomized double-blind trial, 60 obese patients were assigned in groups of 12 to five therapists. The patients for each therapist were then randomly assigned in groups of four to placebo or one of two preparations of mazindol. Ninety-three percent of the patients completed the nine weeks of treatment. Weight loss averaged 1.1 lb per week and there was no advantage to pharmacological agents over placebo. However, there were significant differences between therapists. Weight loss by the patients assigned to physicians was no better than for those assigned to nonphysician personnel, but there were significant differences between individual nonphysician personnel. These findings support the concept that nonphysician personnel may be effective in treating many obese patients. In addition, we could not find a significant effect of either form of mazindol when compared to placebo.

Systemic disorders clearly may exert a significant influence on neuroendocrine function. Disorders that cause significant stress to the body, either physical or psychological, may cause a resetting upward of the HPA axis to provide sufficient cortisol to counteract the stress and to help sustain energy substrate levels. GH levels also increase in many of these situations, again promoting sufficient energy substrate levels. In some circumstances the concomitantly low somatomedin activity may be speculated to be adaptative to prevent the insulin-like agonist activity of these substances as well as to prevent energy expenditure in body growth. However, in other situations such as chronic renal failure and cirrhosis, the decreased somatomedin activity may be primary, causing decreased feedback at the hypothalamic-pituitary level and increased GH levels. The stress-induced rise in PRL may also play a minor role in preserving energy substrate since high levels may promote insulin resistance. In most illnesses the 'euthyroid sick syndrome' develops. Whether such patients are 'euthyroid' or mildly hypothyroid is a matter of controversy. The fact that protein losses are increased during fasting when the lowered T3 levels are returned to normal with exogenous T3 supplementation suggests that these patients are indeed hypothyroid and this hypothyroidism serves to conserve energy substrate by decreasing the metabolic rate. The reproductive axis is often impaired with systemic illness. Again, teleologically this may be viewed as an inactivation of non-essential functions in times of stress. It would appear that the changes that occur with systemic illness, in general, are favourable to the organism in that they promote survival. The detailed neurotransmitter and hypophyseotrophic hormone changes resulting in the alteration in pituitary function remain to be elucidated for the most part.

The authors present the case report of a patient in whom hypopituitarism, diplopia, and visual field defects were due to eosinophilic granuloma. Radiographic studies were suggestive of a pituitary tumor and subsequent histological evaluation showed replacement of the anterior pituitary by histiocytic cells. Eosinophilic granuloma should be included in the differential diagnosis of an intrasellar mass.

To investigate the feedback control of GH secretion, we examined the effects of human GH (hGH) and somatomedin C (SmC) on spontaneous GH secretory surges in unanesthetized, freely moving rats. Under pentobarbital anesthesia a right atrial catheter and an intracerebroventricular cannula were placed 7-10 days before the experimentation. For iv studies, hGH (0.3 U/ml.h) was infused for 6 h after an iv loading dose (0.3 U) at the beginning of the experiments. For intraventricular injections, hGH (0.1 U/10 microliter) or SmC (500 ng/10 microliter) were injected into the lateral ventricle 2 h before the experiments. The equivalent dose of crystalline BSA diluted in the same vehicle solutions was administered to the same rat as a control on a separate day. Venous blood samples were collected every 20 min for 6 h. Intravenous and intraventricular administration of crystalline BSA did not affect the typical rat GH (rGH) surges which appeared about every 3 h and reached peak values of more than 300 ng/ml. The iv infusion of hGH significantly inhibited the amplitude of rGH surges compared to controls (planimetric areas under the secretory profile 752 +/- 172 vs. 1921 +/- 183, P less than 0.01, n = 6). rGH secretion was similarly inhibited by intraventricular hGH (701 +/- 127 vs. 2208 + 225, P less than 0.01, n = 6) and by intraventricular SmC (537 +/- 70 vs. 1503 +/- 114, P less than 0.01, n = 6). These findings suggest that both GH and SmC are active in the feedback regulation of rGH secretion.

Diabetic ketoacidosis is usually accompanied by volume depletion and prerenal azotemia. However, the case reported here and a chart review of 10 patients with diabetic ketoacidosis showed creatinine concentration to be disporportionately elevated compared to the blood urea nitrogen level on admission, compatible with true renal insufficiency. Investigation showed most of this elevation in creatinine to be artifactual and due to interference of acetoacetate in the automated methods for measuring creatinine. A manual method that excluded noncreatinine interfering chromagens showed no interference. This manual method should be used to measure creatinine in patients admitted with ketoacidosis to exclude the possibility of coexistent renal insufficiency.

Prolactinomas are the most common of the hormone-secreting pituitary tumors and must be distinguished from nonsecreting tumors causing hyperprolactinemia by hypothalamic or stalk dysfunction. For both micro- and macroadenomas, dopamine agonists appear to be the treatment of choice, transsphenoidal surgery being reserved for nonresponders. For women desiring pregnancy, dopamine agonists are safe when there is a microadenoma or an intrasellar macroadenoma. However, in women with large macroadenomas desiring pregnancy, limited transsphenoidal decompression followed by bromocriptine appears to be the safest mode of treatment.

To determine whether the abnormalities in dopaminergic regulation of PRL secretion in patients with prolactinomas persist after resection of the adenoma, we evaluated PRL inhibitory responses to L-dopa alone and L-dopa given after pretreatment with the dopa decarboxylase inhibitor carbidopa before and after transsphenoidal selective resection of prolactinomas in 23 women. Eighteen women were cured by surgery (normal PRL, menses, no galactorrhea), while 5 women were not cured. Preoperatively, the PRL inhibitory responses to L-dopa cured, 4 .3 +/- 3.8%; uncured, 50.1 +/- 5.5% of baseline) was blunted by pretreatment with the decarboxylase inhibitor carbidopa (cured, 79.1 +/- 4.1%; uncured, 76.8 +/- 9.2%). Postoperatively, this blunting disappeared in the cured patients (L-dopa, 49.1 +/- 3.5%; carbidopa/L-dopa, 56.3 +/- 5.1%), but the blunting persisted in the uncured patients (L-dopa, 49.3 +/- 7.9%; carbidopa/L-dopa, 69.3 +/- 4.2%). The return to normal of the carbidopa/L-dopa test in cured prolactinoma patients after surgery is evidence that in these individuals, preoperative abnormalities of secretion are due to either intrinsic abnormalities of the tumor or alteration of hypothalamic function secondary to tumor secretion. In those patients not cured by surgery, dynamic tests of function remain abnormal, findings attributable to either incomplete tumor resection or the presence, in some patients, of underlying hypothalamic dysregulation.

The distribution of a substance with human GH (hCG)-like immunoreactivity was studied in the rat brain after rapid fixation with acrolein. Using this method of tissue preparation, the hGH-like material (hGH-LM) was found in several hypothalamic and extrahypothalamic regions of the brain and extended into the spinal cord and posterior pituitary. On serial sections, the distribution of the hGH-LM was observed to be identical to that of TRH throughout the neuraxis. Sequential immunostaining of the hGH-LM and TRH in the same tissue section revealed the coexistence of these two peptides in the same neuronal cell bodies in the hypothalamus and brain stem and in beaded processes in all regions of the central nervous system studied. These findings demonstrate the intimate association between the hGH-LM and TRH in the central nervous system and raise the possibility that the hGH-LM forms part of a precursor hormone from which TRH is derived.

We applied decision analysis to the controversy over the management of the solitary nonfunctioning thyroid nodule. Three standard management plans were considered: immediate subtotal thyroidectomy; a six month trial of thyroid suppression with L-thyroxine, with non-suppressible lesions being removed surgically; and aspiration cytology followed by surgery or thyroid suppression based on the cytologic examination. The literature formed the basis for quantitative assumptions of the analysis, including the consequences of thyroidectomy, the probability of malignancy, the types and prognoses of cancers found at operation, the likelihood of successful suppression adn relapse, and the possible results of aspiration cytology. We used Bayes' rule to revise the probability of cancer on the basis of cytological results. The relative worths of the 59 possible diagnostic and therapeutic outcomes were expressed as quality-adjusted life expectancies. The expected utility of each management plan was determined by "folding back" the decision tree. Although we found that each possible approach yielded a quality-adjusted life expectancy very close to that of the healthy population, aspiration biopsy with cytologic examination appeared slightly superior. Extensive sensitivity analyses demonstrated that either aspiration biopsy or immediate thyroid suppression was the treatment of choice over a wide range of assumptions, although in no case did the benefit exceed 1 year of life. We conclude that all therapies for cold thyroid nodule are essentially equal, viewed in terms of mortality and morbidity. The decision to operate, suppress or aspirate is thus a " tossup ", dependent in the individual case upon such subjective factors as psychological disutility , relative cost, and attitudes toward operative risk and long-term medical therapy. The controversy concerning the "best" management of the cold thyroid nodule is an illusion: quantitative analysis shows the futility of pursuing the debate any further.

CV 205-502 is a nonergot oral dopamine agonist with specific D2 activity, which has a prolonged suppressive effect on serum PRL and may have fewer side-effects than other dopamine agonists. We treated 26 hyperprolactinemic women with this compound given as a single bedtime (hs) dose for up to 12 weeks. All had gonadal dysfunction, either amenorrhea or oligomenorrhea, and 15 had galactorrhea. The initial and subsequent doses were administered in a randomized fashion; the initial dose ranged from 0.01-0.05 mg, and the dose at 12 weeks ranged from 0.03-0.09 mg. The women were evaluated every 2 weeks, and the dose was increased by 0.02 mg every 4 weeks if the serum PRL level was greater than 20 micrograms/L. Of the 26 women initially enrolled, 24 completed 12 weeks of therapy, and 2 discontinued therapy because of side-effects. Thirteen women (54%) had return of menses, and 12 (80%) had either a decrease in or disappearance of galactorrhea. Serum PRL concentrations decreased to a variable degree in all patients; 13 (54%) achieved a normal serum PRL level (less than or equal to 20 micrograms/L). The mean (+/- SE) pretreatment serum PRL concentration was 129 +/- 34, and it was 29.9 +/- 5.9 micrograms/L after 12 weeks of treatment (P = 0.005). The mean (+/- SE) percent reduction in serum PRL was 66.5 +/- 5.0% (median, 78.0%). A dose response was not demonstrated (r = -0.08; P = 0.70) among the 6 dose groups during the last 4 weeks of therapy. In 5 women, serum PRL levels, measured frequently for 24 h after treatment remained low. Side-effects after the initiation of therapy included nausea, headache, and morning fatigue in 10 women. These symptoms caused 2 women to discontinue therapy; they subsided in the other women. An optimal dose was not determined and will probably need to be determined by titration in each patient. CV 205-502, given once daily, appears to be a safe and effective alternative to other dopamine agonists in the treatment of hyperprolactinemia.

Using the peroxidase-antiperoxidase pre-embedding technique for immunoelectron microscopy, human growth hormone (hGH)-like material was demonstrated in large, dense core vesicles in axon terminals in the hypothalamic median eminence of the rat. The close association of immunoreactive terminals with fenestrated capillaries of the portal plexus, suggests that the hGH-like material is contained within the tuberoinfundibular neuronal system and may be a hypophysiotropic hormone.

To determine whether GRH stimulates PRL secretion we studied the effects of iv bolus injections and prolonged infusions of GRH 1-40-OH on PRL and GH serum levels in normal volunteers. Eight patients with acromegaly, two of whom had elevated basal levels of PRL, were also tested with single bolus injections. Six normal subjects given 3.3 micrograms/kg bolus injections of GRH showed a mean increment of GH of 22.0 +/- 1.7 ng/ml (mean +/- SE). A small rise in PRL was noted in 5 of the 6 subjects (mean peak level of 6.4 +/- 1.9 ng/ml vs basal level of 3.3 +/- 0.4 ng/ml, p less than 0.05). During the continuous intusion of GRH (10 ng/kg/min), GH levels rose gradually from a mean baseline of 1.1 +/- 0.1 ng/ml to a mean peak of 30.0 +/- 7.2 ng/ml at about 2 h and then slowly declined to a nadir of 4.2 +/- 0.4 ng/ml at 330 min. PRL levels did not rise significantly during the infusion. To determine whether the decline in GH levels in the face of continued infusion was due to loss of GH responsiveness, a 3.3 micrograms/kg bolus of GRH was given during the nadir at 330 min; this GH increment was significantly less than that obtained by the GRH bolus injection without the infusion (12.9 +/- 3.5 ng/ml vs 22.0 +/- 1.7 ng/ml, p less than 0.05). The PRL response to the GRH bolus was the same during the infusion of GRH as before. In each of 8 acromegalic patients (including two who had initially elevated basal PRL levels) GRH led to an increase in both GH and PRL levels. PRL and GH levels spontaneously fluctuated in parallel in 4 acromegalic cases studied with repeated samples over 6 h during placebo administration. These experiments show that GRH has significant, though weak, PRF effect in normals and that it is more potent PRF in acromegalic patients. Furthermore, the effects on GH and PRL of a sustained infusion of GRH for 5 1/2 h are both qualitatively and quantitatively different. These results suggest that the GRH effect is exerted either on different pituitary receptors for GH and PRL regulation, or that the releasable pools of the two hormones have different sizes and/or turnover times.

A patient with a large pituitary adenoma and visual field loss showed no significant change 6 weeks after transsphenoidal operation, but marked and abrupt improvement occurred at 10 weeks. The implications of this delayed improvement are discussed.

Through use of an antiserum directed against hGH, an immunoreactive hGH-like material has been identified in the rat brain by peroxidase immunohistochemistry. Peroxidase-positive material was found in beaded, neuronal fibers in the external zone of the median eminence, lateral septum, and organum vasculosum of the lamina terminalis and was unaffected by prior hypophysectomy. After pretreatment with intraventricular colchicine, numerous immunoreactive neuronal cell bodies were visualized within the parvocellular medial division of the paraventricular nucleus, periventricular nucleus, dorsomedial nucleus, lateral hypothalamus, and preoptic area. Immunohistochemical staining was completely abolished by preincubation of the antiserum with 10(-6) M hGH, the 20,000 mol wt variant of hGH. hGH dimer, core peptide 20-64/135-167, proteolytically derived hGH fragments 1-134 and 147-91, and human placental lactogen. There was no diminution in staining after preincubation with hGH N-terminal fragment 1-43, hGH C-terminal fragment 171-191, rat GH, rat or human PRL, and numerous other neuropeptides and anterior pituitary hormones. Bilateral electrolytic ablation of the paraventricular nucleus area caused a loss of immunostaining in the median eminence. These results indicate the presence of a hitherto undescribed intrinsic neuronal system in rat brain that contains a substance bearing immunological similarity to the midportion of the hGH molecule and to human placental lactogen. It is proposed that this substance is part of a tuberoinfundibular neuronal system deriving from the parvocellular medial division of the paraventricular nucleus-immunoreactive perikarya and may, therefore, be involved in hypophysial regulation. It may also act as a neuromodulator of limbic lobe structures and other hypothalamic regions.

The use of computed tomography (CT) in 28 patients with surgically proved prolactinomas is described. The authors' experience suggests that in evaluating patients with galactorrhea-amenorrhea syndrome, CT in combination with pluridirectional tomography usually provides sufficient information to make further invasive studies unnecessary. In selected cases with low-density areas within the sella as seen on CT, pneumoencephalography is still advisable to distinguish between the empty sella and the necrotic tumor. Angiography is still necessary to exclude vascular causes for suprasellar and parasellar masses such as aneurysms and meningiomas.

To evaluate the role of the opiate-like peptidergic pathways in modulating the pituitary hormone response to stress, we measured the GH, PRL, and cortisol responses to hypoglycemia and exercise in normal subjects with and without pretreatment with naloxone, given in the centrally active dose of 0.4 mg iv. Basal serum levels of GH, PRL, and cortisol were not changed significantly by prior naloxone administration. The maximum incremental response of GH to exercise was significantly blunted (13.1 +/- 1.6 vs. 6.0 +/- 1.4; P less than 0.001) by prior naloxone administration. Pretreatment with naloxone did not affect the responses of GH, PRL, or cortisol to hypoglycemia or the PRL response to L-dopa. On the basis of these studies we conclude that the opiate-like peptidergic pathways are not important in the regulation of basal levels of GH, PRL, and cortisol and have only a modest modulating influence on the stress-induced release of the hormones, which may be obscured in the face of severe stress.

The specificity of the gonadotropin short-loop feedback mechanism was investigated in castrated rabbits by blood sampling from an indwelling jugular venous catheter for follicle-stimulating hormone (FSH) after the intravenous administration of purified human luteinizing hormone (hLH). Although we have previously shown that such hLH administration results in a decrease of rabbit LH, no decrease in rabbit FSH was seen in these experiments. This specificity of LH feedback is compatible with the site of feedback being at the (1) pituitary level or (2) at the hypothalamic level provided two separate LH and FSH releasing factors exist.

To determine whether VIP functions as a physiological PRL-releasing factor, the effects of immunoneutralization of endogenous vasoactive intestinal peptide (VIP) on the PRL secretory response to suckling and ether stress were assessed. Using a porcine VIP-thyroglobulin conjugate as antigen, a peptide-specific antiserum was generated in a rabbit which bound porcine VIP with a Kd of 5.1 X 10(-11) M and a maximum binding capacity of 1830 ng/ml. In a RIA, this antiserum demonstrated immunoreactive VIP in tissue extracts of various regions of the brain and gastrointestinal tract. IR VIP in extracts of cerebral cortex and hypothalamus coeluted with synthetic porcine VIP on Bio-Gel P-30 column chromatography. Using chronically implanted right atrial catheters for blood sampling to avoid effects of stress and anesthesia, PRL blood levels in normal controls began to rise almost immediately after initiation of suckling from basal values of 3.0 +/- 0.9 ng/ml to reach a plateau of 158.1 +/- 33.5 ng/ml after 40 min. When the VIP antiserum was administered immediately before initiation of suckling, the onset of the PRL response was delayed by 40 min, but PRL levels then rose at a slower rate to reach the plateau level of normal animals approximately 80 min later. When VIP antiserum was administered to rats who had been suckling for at least 1 h, PRL levels fell from a mean basal elevated level of 152.7 +/- 16.0 ng/ml to a nadir of 50.4 +/- 9.1 ng/ml 80 min after injection and then gradually returned to basal levels. The effect of VIP antiserum was studied in rats in whom PRL secretion was increased by exposure to ether, a stimulus that acts on the release phase of PRL secretion. In rats in whom the depletion-transformation of PRL was induced by a prior brief period of suckling, subsequent exposure to ether caused a rise in serum PRL levels. The response was completely blocked in rats given VIP antiserum, whereas animals given nonimmune serum showed a significant increase in serum PRL to 38.6 +/- 17.3 ng/ml. We conclude from these studies that VIP mediates the acute PRL response to suckling and is required for maintenance of PRL levels in continuously suckling animals but is not the only factor causing PRL elevation. Complete abolition by the VIP antiserum of the PRL response to ether indicates that the effect of the anesthetic is mediated entirely by the release of VIP. These findings are consistent with the view that VIP is a physiological PRL-releasing factor in the rat.