The effects of opiate agonist and antagonist on serum prolactin in primates: possible role for endorphins in prolactin regulation.

Intravenous administration of the opiate receptor antagonist naloxone produced a significant reduction in basal serum PRL concentrations in four male Macaca arctoides. Significant decreases from basal levels were found 15, 30, 45, 60, 90, 120, 150, and 180 min after the iv injection of 0.05 and 0.25 mg/kg naloxone. The iv administration of 0.4 mg/kg morphine produced rapid and significant increases in PRL levels, while 0.04 mg/kg morphine or saline produced no change. Both the dopamine receptor-stimulating agent apomorphine (0.15 mg/kg) and naloxone (0.25 mg/kg) decreased basal serum PRL and blocked the morphine-induced increases in serum PRL. These data support the hypothesis that endorphins are involved in the stimulation of PRL secretion.

Hypoglycemia-induced prolactin release.

Recent advances in neurosurgical techniques have made it possible to remove pituitary adenomata with minimal morbidity and mortality. These developments have focused attention on early recognition of pituitary tumors, before the onset of visual disturbances or endocrine dysfunction. We have studied the prolactin response to insulin-induced hypoglycemia as an aid in the evaluation of patients with hypothalamic and pituitary disease. Regular insulin 0.1 units/kg was administered intravenously to normal subjects, to patients with pituitary tumors, and to patients with idiopathic galactorrhea. While the normal subjects regularly showed a prolactin response to hypoglycemia, this was observed infrequently in the other groups. It is possible that prolactin nonresponsiveness to insulin hypoglycemia may reflect nonspecific pituitary damage or may represent an abnormality specific to patients with galactorrhea. Our data suggest that the prolactin response to insulin hypoglycemia is a sensitive index of hypothalamic-pituitary dysfunction.

Effect of piperoxane on serum prolactin: possible role of epinephrine-mediated synapses in the inhibition of prolactin secretion.

Intravenous administration of 2,5 mg/kg piperoxane produced a rapid and significant increase in serum PRL concentrations in four non-human primates. This PRL increase was maximal 15 min after piperoxane infusion and significant, when compared with baseline levels, in the +15, +30, +45, +60, and +90-min samples. The iv administration of 5 mg/kg piperoxane also produced a rapid and significant increase, whereas saline 0.5 mg/kg or 1.0 mg/kg, did not change serum PRL levels. The iv administration of 10 microgram/kg clonidine, but not saline, produced a rapid and significant reduction in serum PRL levels. PRL levels were significantly reduced +15, +30, and +60 min after the clonidine infusion. Pretreatment with a bolus of 10 microgram/kg clonidine at -15 min caused a significant attenuation of the piperoxane-induced elevation in serum PRL in two monkeys. These data support the hypothesis that alpha-adrenergic receptors are involved in the inhibition of PRL secretion. These data are compatible with noradrenergic or adrenergic mechanisms which remain to be defined.

Effect of methylprednisolone upon technetium-99m pyrophosphate assessment myocardial necrosis in the canine countershock model.

Repeat DC countershock reproducibly results in myocardial necrosis in dogs. In this model, myocardial technetium-99m pyrophosphate (PYP) uptake correlates linearly with tissue creatine kinase depletion (r = -0.83). The effect of pretreatment with methylprednisolone (MP) was studied with PYP in 25 dogs. In myocardium damaged by countershock, 12 MP dogs had higher tissue radioactivity sample:normal (S:N) ratios than control (P less than 0.05), suggesting increased tissue injury. However, by several other measures of tissue damage, the two groups did not differ. MP-elevated PYP S:N ratios were explained by reduced PYP activity in normal myocardium of MP dogs. Further experiments in 21 dogs revealed that renal PYP clearance, which correlated with glomerular filtration rate (GFR) as measured by creatinine clearance, was increased in Mp dogs, resulting in accelerated urinary excretion of PYP (46.9+/-3.6 vs 35.8+/-2.4 percent injected dose in one hour, P less than 0.01), and reduced blood PYP. Thus MP does not modify countershock-induced myocardial injury. However, by increasing GFR, MP increased PYP excretion, resulting in lowered blood and normal zone myocardial PYP, thereby spuriously affecting myocardial PYP tissue uptake data.

Hypercalcitoninemia in pancreatitis--evidence for immunochemical heterogeneity.

Recently in our laboratory we have demonstrated increased immunoreactive calcitonin (iCT) levels in 4 patients with acute pancreatitis and hypocalcemia. The present study consists of 17 additional patients in whom serial determinations for (iCT) were performed. Furthermore, with the use of 2 different antisera directed against human calcitonin we present evidence for immunochemical heterogeneity of this hormone in acute pancreatitis.

Pathophysiological correlates of thallium-201 myocardial uptake in experimental infarction.

The pathophysiological correlates of thallium-201 (201TI) myocardial uptake were studied in a 24-hour-old closed-chest canine infarct model. Reduction in regional 201Tl uptake correlated well with the magnitude of tissue creatine phosphokinase depletion and microsphere estimates of transmural blood flow. In low flow endocardial regions 201Tl occasionally under-estimated the magnitude of flow reduction. Even slight reductions of 201Tl uptake (less than 0.86 of normal) were associated with histopathological and histochemical evidence of necrosis.

Effect of increased iodide intake on thyroid function in subjects on chronic lithium therapy.

Thyroid function tests were obtained in 10 patients on chronic lithium therapy before and after the administration of potassium iodide 250 mg q.i.d. Mean serum TSH rose by 8.9 muU/ml and mean serum T3 rose from 70 to 101 ng/dl. Two patients became hypothyroid; a third showed a rise in TSH without any change in T3 or T4. A fourth patient developed hyperthyroidism probably secondary to the Jod-Basedow phenomenon. Pharmacologic doses of iodine should be administered with caution to patients on chronic lithium therapy.

The effect of aspirin and indomethacin on the TRH response in man.

A double-blind study of the effect of two inhibitors of prostaglandin synthesis on the TRH stimulation of serum TSH and prolactin was carried out in 35 normal males. The subjects were evaluated before and after the administration of indomethacin or aspirin for one week. Both indomethacin and aspirin lowered plasma prostaglandin E and F levels significantly. Indomethacin treatment had no effect on the serum TSH or prolactin response to 100 mug TRH or the serum T3 and T4 levels. In contrast, aspirin treatment significantly decreased the serum TSH response to TRH and significantly lowered mean total serum T3 (RIA) and T4 (D). There was no effect on the prolactin response to TRH. These findings suggest that aspirin blocks TRH responsiveness by a mechanism other than the inhibition of prostaglandin synthesis, probably by its previously demonstrated effect on increasing the fraction of unbound thyroid hormone.

Observations on decreased serum glutamic oxalacetic transaminase (SGOT) activity in azotemic patients.

Serum glutamic oxalacetic transaminase (SGOT) activity may be decreased or even absent in patients with uremia. We correlated urea concentration with SGOT activity by the automated Rush (AutoAnalyzer, Techicon Instruments Corp., Tarrytown, New York) method (SGOT, SMA) and by the Henry-Karmen kinetic assay (SGOT, K). Extremely low SGOT (SMA) activity (less than 10 IU) was found in 6% of 5030 consecutive samples, and 71% of them occurred in patients with azotemia. SGOT activity was inversely proportional to urea concentration. A similar but less obvious pattern was observed with the SGOT (K) assay. SGOT activity increased significantly after hemodialysis in a group of 16 patients studied by both methods. It was not inhibited either by urea or uremic serum added in vitro. The explanation for this phenomenon is not known.

Dual radionuclide study of myocardial infarction. Relationships between myocardial uptake of potassium-43, technetium-99m stannous pyrophosphate, regional myocardial blood flow and creatine phosphokinase depletion.

The dual radionuclide myocardial distributions of imaging agents potassium-43 (43K) and technetium-99m stannous pyrophosphate (99mTc-PYP) were studied in a 24-hour closed chest canine infarct preparation. In multiple myocardial biopsies in 20 dogs, tissue levels of both radionuclides were compared to either an index of tissue viability (myocardial creatine phosphokinase [CPK] depletion), or to estimates of regional myocardial blood flow as measured by the microsphere technique. Myocardial 43K uptake in the ischemic and infarcted zone correlated well with both CPK depletion (r = 0.73) and microsphere estimates of relative blood flow. The correlation with microspheres was excellent in the transmural sample (r = 0.93) as well as endocardial (r = 0.97) and epicardial (r = 0.86) portions. On the other hand, 99mTc-PYP myocardial uptake did not correlate with the extent of CPK depletion. Maximal uptake was frequently noted in border zones with only moderate CPK depletion, while lesser degrees of 99mTc-PYP uptake were noted in the central infarct zone where CPK activity was lowest. The relationship of 99mTc-PYP uptake to microsphere regional flow estimates demonstrated that 99mTc-PYP uptake was maximal at flows of 0.3 to 0.4 of normal. At lower flows, 99mTc-PYP uptake fell toward normal levels. A similar relationship was noted between the distributions of 99mTc-PYP and 43K. In relatively high flow border segments (larger than or equal to 0.80 of normal), abnormal 99mTc-PYP uptake of five to six times normal persisted. The transmural distribution of 99mTc-PYP demonstrated that in low flow regions 99mTc-PYP uptake was primarily epicardial, while in the higher flow ischemic periphery of the infarct endocardial uptake predominated. Thus, while there is a direct correlation between cationic 43K myocardial uptake and regional myocardial viability and blood flow, no such direct relationship exists for 99mTc-PYP. This is in part based on the necessity for delivery of the radioactive tracer to the infarct zone.

Hypercalcitoninemia in infancy.

Immunoreactive calcitonin (iCT) was measured in 19 infants with neonatal hypocalcemia. The infants had a variety of neonatal diseases and stresses. iCT levels were generally elevated to two to 20 times the adult values. Poor correlation existed between the infant age and the level of iCT or between iCT alone and the serum calcium. However, there was significant correlation between the serum calcium and the ratio of the iCT to infant age from conception, suggesting that both infant age and iCT levels in combination may be related to hypocalcemia. Also, it appears that a variety of neonatal stresses may be associated with increased sensitivity to the hypocalcemic effect of iCT, as well as increased levels of iCT.

Dopamine infusion acutely inhibits the TSH and prolactin response to TRH.

Ten normal males were given 100 mug TRH, and blood samples obtained for serum TSH and serum prolactin. After a period of at least one week, the TRH test was repeated while the patients were receiving a dopamine infusion. Both the TSH and prolactin response to TRH were inhibited by dopamine. Dopaminergic neurons may act through the pituitary-portal system to play a role in the regulation of TSH and prolactin secretion.

In vitro pituitary responsiveness to gonadotropin-releasing hormone (LH-RH) in intact and castrated male and female rats.

The in vitro response of pituitaries isolated from both normal and 18-21 day post-castration male and female intact rats to incremental doses of synthetic gonadotropin-releasing hormone (LH-RH) has been investigated. Intact male pituitaries released luteinizing hormone (LH) maximally at the smallest dose of LH-RH (0.1 ng/ml) whereas intact female pituitaries released LH in a dose-response fashion. FSH release from intact male pituitaries was considerably greater than that from intact female pituitaries. As with LH, intact male pituitaries appeared maximally stimulated at 0.1 ng/ml of LH-RH. Intact female pituitaries did not release FSH until a 10 ng/ml dose of LH-RH was used. Male and female castrate pituitaries were more susceptible to LH-RH-induced LH and FSH release than were their intact counterparts, although this was more pronounced with regard to LH release. In addition castrate male pituitaries were more sensitive to lower doses of LH-RH than were castrate female pituitaries, this being most pronounced regarding LH release. Castrate female pituitaries released less FSH at the 100 ng/ml dose than at the 10 ng/ml dose, possibly indicating inhibition at these higher doses. In addition, pituitary extraction and serum from normal and castrate male and female rats were examined for LH and FSH content. LH content of castrated rat pituitaries of both sexes was considerably greater than that of their intact counterparts, as expected. However, castrate male pituitaries contained significantly less FSH than intact male pituitaries, whereas the opposite was true for the female groups. Serum LH and FSH levels were increased in the castrate groups with no difference between sexes. Serum from intact males contained considerably more FSH than did the serum from intact females.