PRL Values Research Articles

Pituitary imaging is indicated for the evaluation of hyperprolactinemia

To evaluate the signs and symptoms associated with hyperprolactinemia and establish guidelines for a minimal serum PRL level for which pituitary imaging is indicated. Retrospective study. Reproductive endocrinology clinic in a university hospital. One hundred four consecutive patients with hyperprolactinemia, mean age 30 +/- 6.5 (range 19-44) years. Classification of clinical symptoms, serum hormone measurements, and pituitary magnetic resonance imaging (MRI). Incidence of presenting symptoms, serum PRL levels, and pituitary tumor size. Median (range) PRL value was 82.6 ng/mL (25-1,342). Reported symptoms from most to least common were infertility (48%), headaches (39%), oligoamenorrhea (29%), galactorrhea (24%), and visual changes (13%). Hypothyroidism was diagnosed in 2 of 104 (1.9%) patients. Of 86 patients who had pituitary imaging, 23 (26%) had normal findings and 63 (74%) had pituitary tumor; of these, 47 (55% of total imaged) had microadenomas and 16 (19% of total imaged) had macroadenomas. There was a statistically significant association between the tumor size and the PRL level. However, 11% of the patients with microadenomas had PRL levels >200 ng/mL, and 44% of the patients with macroadenomas had PRL levels between 25 and 200 ng/mL. The most common symptoms in the population studied were infertility and headaches. Coexisting thyroid disease was an uncommon finding. Most patients had a pituitary tumor on MRI. Although tumor size correlated with the serum PRL level, some macroadenomas were detected in women with only moderately elevated PRL values. On the basis of these findings, pituitary imaging should be obtained to identify pituitary tumors in all patients with persistently elevated PRL levels.

Prevalence of osteopenia in men with prolactinoma

The aim of this cross-sectional study was to analyze bone mineral density (BMD) and prevalence of osteopenia and osteoporosis in 30 men with prolactinoma, and compare them to 22 control subjects. BMD of lumbar spine and femur was evaluated by dual-energy X-ray absorptiometry. PRL, testosterone, estradiol, sexual hormone-binding globulin and free androgen and estrogen indexes (FAI and FEI, respectively) were measured in all the subjects. In patients with prolactinoma, mean values of PRL and testosterone were calculated for the 12-month period that preceded the study. The mean T-score of the four sites analyzed by bone densitometry was lower in men with prolactinoma than in controls (p-values: lumbar spine=0.015, femoral neck <0.0001, trochanter=0.037, total femur=0.036), and 55.6% of the former presented osteopenia or osteoporosis at one or more sites (p =0.035). The lumbar spine was the most seriously affected site, where 29.6% had osteopenia and 14.8% had osteoporosis. By the time of BMD determination, significant associations were found between BMD and PRL, testosterone, FAI, estradiol, FEI, and duration of hypogonadism. Considering the period of 12 months that preceded BMD evaluation, trochanter BMD was associated with mean PRL levels, while there was an association between lumbar spine BMD and mean testosterone levels. However, the multiple regression analysis showed that estradiol was the main determinant of BMD. In conclusion, men with prolactinoma have high prevalence of osteopenia and osteoporosis. Bone loss in such patients is associated with hyperprolactinemia and hypogonadism, and mainly influenced by estrogen.

Identification of IgG-immunocomplex macroprolactin with an immunometric “sandwich” system: Technical and clinical considerations

MacroPRL can be due either to anti-PRL autoantibodies IgG (IgG-macroPRL) or other PRL containing molecules without IgG-PRL immuncomplexes (nIgG-macroPRL), the composition of which is not fully clarified. The aims of this study were: a) testing a new immunometric assay, capable of recognising IgG-macroPRL, b) looking for any biological and/or clinical discrepancy between nlgG-macroPRL and IgG-macroPRL. Clinical, biological and neuroradiological data were recorded from 28 hyperprolactinemic women classified as macroprolactinemic on the basis of PRL recoveries after polyethylene glycol (PEG) precipitation <50% on a Roche Elecsys analyser. Fourteen sera with recoveries >70% were employed as controls for the IgG-macroPRL assay. An immunometric "sandwich" assay for IgG-macroPRL was performed employing an anti-PRL antibody to capture PRL and a second one binding and tracing the immunoglobulin G (IgG) component. For this purpose, 2 kits were simultaneously employed, the first for PRL assay and the second for Anti-Toxoplasma IgG assay. The procedure was applied to both DiaSorin LIAISON and Abbott AxSYM systems. IgG-macroPRL immunometric detection was obtained with DiaSorin LIAISON. Twenty out of 28 (72%) sera gave luminescent signal higher than the maximum control serum and were considered as IgG-macroPRL carriers. Our results confirm the high IgG-macroPRL prevalence in macroprolactinemia. No significant clinical differences appear between IgG and nIgG-macroPRL. Conversely, significantly higher PRL values (p =0,039) and lower recoveries (p = 0.001) were found in IgG-macroPRL. Further studies with reference methods, such as gel chromatography and human IgG (h-IgG) affinity columns, are needed to fully validate this IgG-macroPRL immunometric assay.

Lack of relevant association between prolactin and immune responses in patients with chronic heart failure

Recently an association between decreased activation of T-lymphocytes reflected by hyperprolactinemia and left ventricular systolic function in CHF has been suggested. PRL is a pluripotent hormone which interferes with immune regulation as well as angiogenesis. Furthermore, PRL enhances platelet activation, especially CD62p expression. In our series of 50 patients with CHF (66.9±12.6 years; EF: 22±9%), we demonstrated significantly reduced serum levels of IL-10, an anti-inflammatory cytokine, revealing the inflammatory milieu in CHF. To further elucidate the influence of hyperprolactinemia in CHF on platelet activation we retrospectively studied PRL values in the sera of our patients and compared these results with CD62p expression on platelets. In contrast to previous findings we detected no hyperprolactinemia in our CHF patients (PRL: 6.2±4.3 ng/ml, normal range of our assay: in females <24.2ng/ml and in males <18.7ng/mL). There were no significant differences between patients with EF>30% (n=19; PRL: 5.6±3.2 ng/ml) and EF<30% (n=31; PRL; 6.5±4.8 ng/ml; p>0.05). Moreover, we found no significant correlation between PRL and left ventricular function (r2=-0.008; p>0.05) and the pro-inflammatory cytokines IL-6 (r2=0.036; p>0.05), TNFa (r2=0.0034; p>0.05) or the anti-inflammatory cytokine IL-10 (r2=0.002; p>0.05). However, patients with CHF showed significant enhanced expression of CD62p on platelets compared to healthy control subjects. CD62p was not correlated to PRL values (r2=-0.012; p>0.05). This finding contrasts to our results in other patient-groups but can be explained by the low PRL values in our patients with CHF. Therefore, our data suggest that PRL- independent activation of the pro-inflammatory milieu in CHF may play a pathogenic role in the development and progression of CHF. In conclusion, PRL was neither associated with left ventricular function nor correlated with pro- or anti-inflammatory cytokines in CHF patients.

A transgenic mouse with a deletion in the collagenous domain of adiponectin displays elevated circulating adiponectin and improved insulin sensitivity.

Adiponectin is a plasma protein expressed exclusively in adipose tissue. Adiponectin levels are linked to insulin sensitivity, but a direct effect of chronically elevated adiponectin on improved insulin sensitivity has not yet been demonstrated. We identified a dominant mutation in the collagenous domain of adiponectin that elevated circulating adiponectin values in mice by 3-fold. Adiponectinemia raised lipid clearance and lipoprotein lipase activity, and suppressed insulin-mediated endogenous glucose production. The induction of adiponectin during puberty and the sexual dimorphism in adult adiponectin values were preserved in these transgenic animals. As a result of elevated adiponectin, serum PRL values and brown adipose mass both increased. The effects on carbohydrate and lipid metabolism were associated with elevated phosphorylation of 5'-AMP-activated protein kinase in liver and elevated expression of peroxisomal proliferator-activated receptor gamma2, caveolin-1, and mitochondrial markers in white adipose tissue. These studies strongly suggest that increasing endogenous adiponectin levels has direct effects on insulin sensitivity and may induce similar physiological responses as prolonged treatment with peroxisomal proliferator-activated receptor gamma agonists.

PRL as a Novel Potent Cofactor for Platelet Aggregation

Pregnancy (including puerperium) is a period of hypercoagulability and seems to be an independent major risk factor for venous thromboembolism (VTE). However, the basis of the increased risk of VTE in pregnancy and around delivery is unknown. We hypothesized that changes in PRL, which is a prominently increased hormone during pregnancy and lactation, might be involved in the activation of platelets. To investigate platelet functional abnormalities in pregnancy, we assessed the ADP-stimulated and nonstimulated P-selectin expression of platelets in 42 consecutive pregnant women, 22 normo- and hyperprolactinemic patients with pituitary tumors, and controls. In addition, the aggregation of platelets by human PRL in vitro was studied. We found a significant correlation between PRL values and ADP stimulation of platelets in pregnant women (r = 0.56; P < 0.0001) and patients with pituitary tumors (r = 0.57; P = 0.006). Hyperprolactinemic pregnant women or hyperprolactinemic patients with pituitary tumors revealed significantly higher ADP stimulation of platelets (P < 0.0001) than healthy controls or normoprolactinemic patients with pituitary tumors. These results were reconciled by increased in vitro stimulation and aggregation of platelets using human PRL. Our novel findings demonstrate that hyperprolactinemia causes increased platelet aggregation via ADP stimulation both in vitro and in vivo. Moreover, our data indicate that PRL may be a physiological cofactor of the delicate coagulation balance during pregnancy and puerperium that might explain the increased risk of VTE in pregnant women around delivery. Further studies of the interaction between PRL and platelets will clarify the clinical relevance of hyperprolactinemia as a potential risk factor for VTE.

PRL as a novel potent cofactor for platelet aggregation.

Pregnancy (including puerperium) is a period of hypercoagulability and seems to be an independent major risk factor for venous thromboembolism (VTE). However, the basis of the increased risk of VTE in pregnancy and around delivery is unknown. We hypothesized that changes in PRL, which is a prominently increased hormone during pregnancy and lactation, might be involved in the activation of platelets. To investigate platelet functional abnormalities in pregnancy, we assessed the ADP-stimulated and nonstimulated P-selectin expression of platelets in 42 consecutive pregnant women, 22 normo- and hyperprolactinemic patients with pituitary tumors, and controls. In addition, the aggregation of platelets by human PRL in vitro was studied. We found a significant correlation between PRL values and ADP stimulation of platelets in pregnant women (r = 0.56; P < 0.0001) and patients with pituitary tumors (r = 0.57; P = 0.006). Hyperprolactinemic pregnant women or hyperprolactinemic patients with pituitary tumors revealed significantly higher ADP stimulation of platelets (P < 0.0001) than healthy controls or normoprolactinemic patients with pituitary tumors. These results were reconciled by increased in vitro stimulation and aggregation of platelets using human PRL. Our novel findings demonstrate that hyperprolactinemia causes increased platelet aggregation via ADP stimulation both in vitro and in vivo. Moreover, our data indicate that PRL may be a physiological cofactor of the delicate coagulation balance during pregnancy and puerperium that might explain the increased risk of VTE in pregnant women around delivery. Further studies of the interaction between PRL and platelets will clarify the clinical relevance of hyperprolactinemia as a potential risk factor for VTE.

Neuroendocrine correlates of temperamental traits in humans.

Studies investigating temperament traits in humans and their biological correlates have found high levels of novelty seeking (NS) linked with dopaminergic system changes, and particularly a deficit of dopamine transporter. Harm avoidance and reward dependence, on the other hand, appeared to be associated, respectively with serotonin and noradrenaline changes. In the present study, we have investigated the dopaminergic (DA), serotonergic (5-HT), and noradrenergic (NE) functions in healthy volunteers by challenging the monoamine systems with the DA agonist bromocriptine, the 5-HT agonist D-fenfluramine, and the NE agonist clonidine, respectively. Parallel to this investigation, we examined the temperament traits of our subjects by measuring NS, harm avoidance (HA) and reward dependence (RD) using the 'Three-dimensional Personality Questionnaire' (TPQ). The aims of the study were to see whether or not the monoamine functions were correlated with temperament traits. Bromocriptine challenge induced a significant GH increase and a significant suppression of PRL. D-fenfluramine test significantly increased PRL and cortisol plasma levels and Clonidine test induced a significant rise in GH values. NS scores showed a significant direct correlation with brom-stimulated GH values (r=0.426, P<0.05) and a significant inverse correlation with brom-inhibited PRL values (r=-0.498, P<0.01). HA scores correlated significantly with D-fen-stimulated PRL and CORT AUCs, (PRL: r=0.424, P<0.05; CORT: r=0. 595, P<0.005). RD scores correlated positively with clon-stimulated GH values (r=0.55; F=8.6; P<0.01) and negatively with brom-inhibited-PRL AUCs (r=-0.439, P<0.05). Our data support Cloninger theory concerning the biological correlates of temperamental traits, and evidence the link between the neuroendocrine responses to dynamic challenges and stable temperament features.

Diurnal changes in plasma prolactin during the last one third of pregnancy in the baboon.

Previous studies in our laboratory revealed that daily plasma prolactin (Prl) levels were higher in the evening than in the morning in the pregnant baboon suggesting a diurnal variation. The goal of this study was to examine in more detail the diurnal alterations in plasma Prl levels. A tethered pregnant baboon model was utilized for these studies. Hourly venous blood samples were taken from 0700 to 2400 hr (n=10) or until 0700 hr the following day (n=5). The studies were performed at various days of pregnancy from day 135 until delivery. Plasma samples were analyzed for Prl by radioimmunoassay. A surge in plasma Prl was detected, starting around 1500 to 1600 hr and lasting for 3 to 5 hr. The surge occurred before the lights went off in the colony (1800 hr). Baseline Prl levels were higher in animals < 15 days before delivery compared to those > 15 days before delivery (P < 0.05). In contrast, no differences were found in the average peak Prl values between these two groups of animals. In summary, in the pregnant baboon during the last one-third of pregnancy plasma Prl surges, beginning around 1500 to 1600 hr and lasting for 3 to 5 hr. Less than 15 days before delivery the mean baseline Prl levels are higher compared to animals greater than 15 days before delivery.

Secondary adrenal insufficiency associated with autoimmune disorders: a report of twenty-five cases.

Addison's disease is frequently a component of autoimmune polyendocrinopathies while secondary adrenal insufficiency associated with autoimmune disorders is believed to be a rare event. We present a series of patients with secondary adrenal insufficiency coexisting with autoimmune diseases and/or antithyroid autoantibodies. Among a group of 102 patients with secondary adrenal failure of unknown origin diagnosed at the Department of Endocrinology of the Centre for Postgraduate Medical Education (Warsaw, Poland) we have identified a group with associated autoimmune disorders. Thyroid abnormalities occurred most frequently. Other diseases included insulin-dependent diabetes mellitus, pernicious anaemia, vitiligo, premature ovarian failure and autoimmune thrombocytopaenia. There were 23 women and one man aged 17-72 years at the time of investigation. Additionally, we included a woman with Addison's disease in whom the ACTH deficiency appeared 18 years after the onset of primary adrenal hypofunction. Pituitary-adrenal function tests comprised urinary excretion of 17-hydroxycorticosteroids in basal conditions and during a 2-day tetracosactrin test, plasma concentrations of ACTH and cortisol, and a 2-day metyrapone test (in eight cases). Thyroid function and immunity tests were: TSH, thyroxine, the antithyroglobulin, antimicrosomal and anti-peroxidase autoantibodies. Other endocrine studies included: serum LH, FSH and PRL. The 17-hydroxycorticosteroid values, both basally and during stimulation tests were consistent with a diagnosis of secondary adrenal insufficiency. Serum cortisol and plasma ACTH concentrations were low. In 14 patients primary hypothyroidism was confirmed by low T4 levels. In three patients subclinical primary hypothyroidism was revealed (elevated TSH levels). Three patients who had a past history of Graves' disease were euthyroid at the time of investigation. Twenty-three patients had antibodies against peroxidase. Most patients had gonadotrophins and PRL values within normal limits. The co-existence of autoimmune disorders with secondary adrenal insufficiency suggests an autoimmune aetiology for the ACTH deficiency.

Frequency of hyperprolactinaemia due to large molecular weight prolactin (150-170 kD PRL).

Of 605 hyperprolactinaemic sera (prolactin > 1000 mU l-1 determined with PRL DELFIA, Wallac) in the routine diagnostic (PRL was measured in 10,737 sera) 26% had an increased amount of PRL with molecular weight (MW) = 150-170 kD (150-170 kD PRL or bigbig PRL). In a series of serum samples from 660 healthy subjects, only one female with hyperprolactinaemia due to increased 150-170 kD PRL was found. The 150-170 kD PRL constituted less than 1% of the total PRL found in 11 patients with prolactinoma (macroprolactinoma, PRL 8800-500,000 mU l-1). When determined with five different commercially available immunometric assays, the PRL values in the sera with large amounts of 150-170 kD were increased in all sera in four of five assays, although they varied widely. The clinical implications of hyperprolactinaemia due to increased 150-170 kD PRL are still uncertain.

Modulation of prolactin receptors in the rat hypothalamus in response to changes in serum concentration of endogenous prolactin or to ovine prolactin administration

Specific binding of 125I-labeled rat prolactin ( 125I-rat PRL) to hypothalamic membranes was studied in Sprague-Dawley rats after ovine PRL administration and in relation to rat PRL serum variations induced by ectopic pituitary implants or by drugs which stimulate (domperidone) or inhibit (bromocriptine) PRL release. Repeated treatments with ovine PRL markedly increased specific binding values of 125I-rat PRL to hypothalamic membranes of female rats. Repeated treatments with domperidone also increased specific PRL binding in the hypothalamus. This effect was associated with an increase in PRL serum levels. Similar results were obtained in male rats after renal pituitary implants which resulted in a state of chronic hyperprolactinaemia. In contrast, a subchronic treatment with bromocriptine decreased specific PRL binding in the hypothalamus and concomitantly caused a sharp reduction in PRL serum levels. Scatchard analysis of data obtained from competition curves showed that the variations in the level of PRL binding to hypothalamic membranes were related to the number of PRL binding sites but not to the dissociation constant ( K d), which unaffected by different treatments or by pituitary implantation. These results demonstrate a correlation between circulating concentrations of PRL and number of its receptors in the rat hypothalamus and give further support to the hypothesis that these binding sites may have a specific functional role in regulating the homeostasis of pituitary PRL secretion.

Effects of anti-prolactin autoantibodies on serum prolactin measurements

The influence of anti-PRL autoantibodies on PRL measurements determined by immunoassays was investigated in 10 patients with anti-PRL autoantibodies. Four different immunoassay systems (two double-antibody radioimmunoassays (RIAs), a single-antibody RIA and an immunoradiometric assay (IRMA)) were examined. Total and free PRL were extracted from sera by precipitating gamma-globulin with polyethylene glycol with and without acidification, respectively. PRL values determined by direct measurement were compared with total PRL values. The proportion of free to total PRL levels determined by each immunoassay in sera with anti-PRL autoantibodies was significantly lower than in control sera. Values obtained by direct measurement of PRL (a routine assay procedure) in control sera were similar to total PRL values, whereas in sera with anti-PRL (a routine assay procedure) in control sera were similar to total PRL values, whereas in sera with anti-PRL autoantibodies the values varied from one immunoassay to the other. In sera with anti-PRL autoantibodies, double-antibody RIA 1, RIA 2 and single-antibody RIA 3 yielded values lower for PRL than for total PRL (52 +/- 15% in RIA 1, 40 +/- 8.8% in RIA 2, 40 +/- 14% in RIA 3), while PRL levels determined by IRMA were not significantly different (112 +/- 14%). Immunoglobulin G purified from serum with anti-PRL autoantibodies dose-dependently decreased the recovery of PRL assayed by the double-antibody technique, while it did not affect that by IRMA. These data suggest that the presence of anti-PRL autoantibodies gives variable results depending on the immunoassays used.(ABSTRACT TRUNCATED AT 250 WORDS)

Hormonal and radiological effects of megavoltage radiotherapy in patients with growth hormone-secreting pituitary adenoma.

Nineteen acromegalic patients (12 females and 7 males, aged 24-71 yr) were studied for 1-6 yr after radiotherapy (RT), administered by X-rays (18 MeV) by linear accelerator, with parallel opposite beams (doses 45-50.4 Gy, 1.8 Gy daily). Basal GH levels gradually decreased from 6.3-76.2 micrograms/L (mean +/- SE, 27.8 +/- 4.9) to 0.3-43.4 micrograms/L (11.7 +/- 3.6 micrograms/L; p < 0.005) at the last assessment. The earliest significant decrease was observed after one yr (14.9 +/- 3.8 micrograms/L; p < 0.005). Significant changes were observed also in IGF-I values (basal values 1.93-6.85 mU/ml, 3.22 +/- 0.30; last assessment 0.55-4.57 mU/mL, 1.58 +/- 0.31; p < 0.01). The earliest significant decrease of IGF-I values was observed after 2 yr (1.61 +/- 0.16 mU/ml; p < 0.005). GH levels < 5 micrograms/L together with normal IGF-I values were observed in 9 patients, 2-4 yr after RT. No changes were observed in PRL values, either in patients with pretreatment normal or elevated PRL levels. The CT and/or MRI picture of macroadenoma disappeared after 6-12 months in 3/12 patients. Moreover, a reduction (20-55%) in the diameter of the adenoma was shown after 6-36 months in other 4 patients. After RT 5/16 (31%) patients required cortisol and 4/19 (21%) thyroid replacement therapy. In 2/3 men a gonadal impairment was shown, that did not occur in the three female patients with normal gonadal function before RT.(ABSTRACT TRUNCATED AT 250 WORDS)

PROLACTIN (PRL) SECRETION OF PERMATURE AND FULL-TERM NEONATES IN NORMAL AND VARIOUS PATHOLOGICAL. CONDITIONS

To investigate the physiological role of PRL in early life, we have studied serum PRL concentrations longitudinally in large cohort of premature and full-term neonates in normal and pathological conditions.We have studied serum PRL in full-tem neonates (n = 84), premature neonates(n=50), those of amniotic fluid (n=29) and umbilical cord specimen. We also studied serum PRL in children with dehydration(n=30) before and after fluid therapy, Serum PRL has been measured by immunoradiometric assay, using newly developed one-step solid phase PRL assay kit.Full-term neonates revealed high PRL in male (156.4 ± 74.1ng /ml) and in female (178.4 ± 74.1ng/ml) and these high PRL values immediatley after birth gradually fell over one to four months postnately after birth gradually fell over one to four months postnatally. Small for date(SFD) premature neonates at 31-36 weeks showed significantly higher PRL, compared to those of appropriate for date(AFD), but no significant difference was noted in SFD and AFD full-term neonates. Significantly higher PRL was found in asphyxia of full-term neonates, but not in those of premature infants. Increased PRL in children with dehydration revealed significant decrease after fluid replacement therapy.We have extensively studied serum PRL in perinatal period in normal and various pathological conditions, because PRL has numerous and diverse actions. This study appeared to be the first report of ontogenesis of prolactin secretion in the fetus, neonates and infants in the largest series. The meaning of high PRL in the perinatal period remitins to be elucidated.

Effects of the Dopamine Agonist CV 205–502 in Human Prolactinomas Resistant to Bromocriptine

In 21 patients with prolactinomas resistant to bromocriptine, we studied the effects of CV 205-502 on PRL hypersecretion and tumor mass, as assessed by consecutive computed tomography examinations. Cell culture studies were performed in 9 of such tumors. In 11 patients (group I; 52%) with a mean baseline plasma PRL level of 468 +/- 160 micrograms/L (+/- SE), normal PRL values were achieved after 1-6 months of treatment with 0.1-0.5 mg/day CV 205-502. Tumor size was reduced by 25% or more in 6 of 11 patients. In group II (n = 10), PRL levels (948 +/- 538 micrograms/L at baseline) were reduced by 48% after treatment with 0.1 mg/day CV 205-502. A progressive increase in the daily dose up to 0.5 mg did not further improve the partial reduction of PRL. No reduction in tumor size was observed in this group. The cell culture studies showed that 1) a brief exposure to both drugs provoked PRL suppression lasting 3 days; 2) in group I, CV 205-502 suppressed PRL release more efficiently than bromocriptine, with a ma...

The Brain Renin-Angiotensin System and Prolactin Secretion in the Male Rat*

The present studies investigated the role of the brain renin-angiotensin system in the regulation of PRL secretion in the male rat. Blood samples were taken from conscious rats before, during, and after administration of test substances into the third cerebral ventricle. In the first series of experiments, we determined the sensitivity of the PRL response to intracerebroventricular (icv) administration of angiotensin II (Ang II) and found that PRL levels were significantly suppressed in a dose-related manner (10-500 ng). A dose of 1 ng did not significantly affect PRL values, compared to those from vehicle-injected animals. Ang II elicited water intake at doses of 50 and 500 ng, but not at the 10- or 1-ng doses. In the second series of experiments, we investigated the role of endogenous brain Ang II in the regulation of PRL secretion under basal and stimulated conditions. The endogenous system was manipulated by icv infusion of saralasin, an Ang II receptor antagonist, or icv injection of enalaprilat, a converting enzyme inhibitor, to prevent synthesis of Ang II. Neither saralasin nor enalaprilat administration produced an increase in PRL levels under basal, nonstressed conditions. However, during immobilization stress, when PRL levels increased 3-fold during icv vehicle infusion, saralasin infusion resulted in a 7-fold rise in plasma PRL titers relative to prestress baseline values. These results demonstrate that, in male rats, the inhibitory effects of icv administration of Ang II on PRL secretion are very sensitive and are observed at doses which do not affect water intake. The endogenous brain Ang II system appears not to be involved in the maintenance of the low plasma PRL levels observed under basal, nonstressed conditions. However, the system does appear to affect the magnitude of the PRL response to immobilization stress.

Effects of Uncomplicated Acute Myocardial Infarction on Biochemical Parameters of Stress and Sexual Function

The blood levels of several "stress indicators" (prolactin [PRL], growth hormone [hGH], total catecholamines, and adenosine 3',5'-cyclic monophosphate [cAMP]) were measured in men during the first 2 weeks of uncomplicated acute myocardial infarction (AMI) and during a 3-month follow-up period. PRL levels were significantly elevated during the first day, and hGH was elevated during the week after the AMI. The levels returned to the control baseline values thereafter. The levels of the total catecholamines and cAMP in blood remained normal throughout the study period. Sexual function during the 3-month follow-up was measured in 29 patients, using a specially designed questionnaire. Impotence was found in five patients and decreased libido in four. No correlation was noted between PRL values, the other stress indicators, and sexual dysfunction. A trend toward increased incidence of sexual dysfunction was found among patients with recurrent AMI.

Altered growth hormone response after growth hormone releasing hormone administration in chronic renal failure

Eleven chronic renal failure patients and 11 matched controls, received growth hormone GHRH (1 microgram/kg iv) or TRH (400 microgram iv) on separate occasions, immediately before undergoing hemodialysis. GHRH-induced GH peak in uremics (22.7 +/- 5.2 micrograms/l) was not different from that obtained in control subjects (16.0 +/- 4.3 micrograms/l). However, the uremic patients did not show the habitual post-peak fall, remaining GH levels over 10 micrograms/l till the end of the test. Differences between the two groups were significant (p less than 0.05). Uremic patients showed PRL values higher than in controls, however their TRH-induced PRL peak (20.6 +/- 6.6 micrograms/l) was not different from that of controls (26.5 +/- 3.0 micrograms/l). Again chronic renal failure patients showed PRL plasma values abnormally elevated till the end of the test. Differences between the two groups were significant (p less than 0.05). Administration of placebo to a different group of seven uremic patients did not alter GH and PRL plasma levels. This sustained secretion of both GH and PRL in uremia could be attributed to reduced kidney clearance. However, when subjects were examined individually both the GHRH- and the TRH-induced hormonal peaks and the subsequent fall were not different in both groups. Unlike with controls, in uremic patients GHRH-stimulated GH and TRH-stimulated PRL/GH peaks were dispersed throughout the 120 min period. In controls GH and PRL peaks clustered around 15-30 min. The peak dispersion created a false impression of flattened curves or sustained hypersecretion in uremia.(ABSTRACT TRUNCATED AT 250 WORDS)

Circadian, ultradian, and episodic gonadotropin and prolactin secretion in human pseudocyesis

Six women with pseudocyesis were studied by 15-min blood sampling for 12 to 24 h to determine their gonadotropin and PRL secretory profiles aiming to clarify the endocrine alterations in this form of hypothalamic amenorrhea. Clinical and biochemical evidence of hyperandrogenism was found in 4 patients. Persistent hyperprolactinemia was present only in one patient. Significant circadian and ultradian periodicities were identified by time series analysis in the 12-24 h profiles of FSH, LH and PRL secretion. Pulse analysis by the Van Cauter (UL-TRA.JN) method revealed a 24-h mean LH interpulse interval of 91 +/- 21 min with a mean LH amplitude of 5.4 +/- 0.8 IU/l. There was a significantly lower pulse frequency at night than during the daytime. The mean 24-h PRL interpulse interval and pulse amplitude were 134 +/- 22 min and 9.2 +/- 1.8 IU/l, respectively. Both FSH and LH mean levels were higher during the daytime than at night, while the reverse was true for PRL values. Decreased LH pulse frequency and amplitude emerged as the most distinctive findings. Antecedent hypothalamic-pituitary aberrations due to other endocrinopathies and the timing of the hormonal assessment (e.g. recovery phase) may explain, at least in part, the reported heterogeneity of neuroendocrinologic findings in pseudocyesis.