Basal serum prolactin levels and prolactin responses to constant infusions of thyrotropin releasing hormone in healthy aging men

We measured serum prolactin (PRL) levels by RIA before and during a 240-min constant infusion of TRH (0.4 microgram/min iv) in three similarly sized groups of healthy aging men 30 to 49, 50 to 69, and 70 to 96 years. Basal data were evaluated by analysis of variance with Duncan's multiple range test and regression analysis. Mean basal serum PRL level was elevated (p less than .05) in the oldest group, attributable to PRL elevations (between 20 and 40 ng/ml) in 4 men over 75 years. Serum PRL levels decreased (p less than .001) from -30 min to 0 min before TRH infusion in all groups, but there was no age-dependent difference (p greater than .3) in the magnitude of the reduction. Repeated measures analysis of variance showed increased serum PRL levels (p less than .001) during TRH infusion in all age groups, and an age-dependent increase (p less than .05) in magnitude of peak PRL response. This significant difference was between the two oldest age groups early in the infusion. Chi-square analysis revealed an increased (p less than .05) frequency of early (less than 120 min) peak responses in the oldest age group. The present data suggest that basal and TRH-stimulated PRL secretion may be augmented in some healthy older men.     

Lack of dissociation of prolactin responses to thyrotropin releasing hormone and metoclopramide in chronic alcoholic men

Prolactin, growth hormone and thyroid stimulating hormone responses to thyrotropin releasing hormone (TRH) and metoclopramide were determined in 12 alcoholic men with biopsy proven liver disease and were compared to those of 8 age matched normal controls. All subjects were challenged with TRH (400 micrograms) and metoclopramide (10 mg) given as an intravenous bolus each on a separate day. Alcoholics had increased basal prolactin and growth hormone levels compared to controls. Alcoholics had a brisk and statistically significant (p less than 0.01) response for each of the 3 hormones studied in response to TRH. In contrast to the alcoholics, the controls did not demonstrate a growth hormone response to TRH. Moreover, the TSH response to TRH of the alcoholics was exaggerated (p less than 0.05) compared to that of the controls. In response to metoclopramide, alcoholics had a brisk prolactin response, failed to demonstrate a TSH response, and had a decline in growth hormone when compared to controls. These results for alcoholics with liver disease differ from those reported for individuals with renal failure while those for the controls are similar to previously reported normal responses. These data suggest that liver disease and renal disease must differ in terms of their patterns of hypothalamic-pituitary neuroregulation as documented by their differing pituitary hormone responses to TRH and metoclopramide.     

Apomorpine inhibits the prolactin but not the TSH response to thyrotropin releasing hormone.

Pretreatment of normal subjects with apomorphine, a dopamine receptor agonist, resulted in significant impairment of the subsequent prolactin (PRL) response to thyrotropin releasing hormone (TRH). The mean maximal increment of PRL was 27.9+/-2.4 ng/ml after TRH alone, and 11.9+/-3.0 ng/ml (P less than 0.001) after apomorphine plus TRH. In contrast, the.thyrotropin (TSH) response to TRH was unaffected by apomorphine (10.5+/-2.9 vs. 9.5+/-1.8 muU/ml, P greater than 0.5). These results demonstrate that dopaminergic effects are capable of inhibiting PRL responses to TRH, probably via a direct effect on the lactotrope cell. They also suggest that dopaminergic influences are not important in the regulation of TSH secretion.     

Prolactin responses to vasoactive intestinal polypeptide and thyrotropin releasing hormone in chronic renal failure.

Prolactin response to iv bolus injection of 1 micrograms/kg vasoactive intestinal polypeptide was determined in 8 patients with chronic renal failure undergoing chronic hemodialysis and in 8 normal controls, age- and sex-matched. Plasma prolactin in the patients showed a blunted response following vasoactive intestinal polypeptide injection, whereas the controls showed significantly higher mean peak prolactin value over the baseline value (p less than 0.002). The net rise (peak levels minus basal levels) in plasma prolactin and area under the curve after vasoactive active intestinal polypeptide injection in the controls were significantly greater than those in the patients (p less than 0.001). On a separate day, each individual underwent a TRH (500 micrograms) challenge with the prolactin response determined. The patients had significantly higher peak prolactin values over baseline levels (p less than 0.02) which, however, were not significantly different from those in the control group. In the patients, the peak net prolactin increments and area under the curve were significantly higher following TRH than following vasoactive intestinal polypeptide (p less than 0.05). The net prolactin increments to TRH challenge were significantly higher in the control group than in the patients (p less than 0.001). The results demonstrate the blunted prolactin response to the stimulatory effect of vasoactive intestinal polypeptide and TRH in chronic renal failure. In chronic renal failure prolactin release after vasoactive intestinal polypeptide is more blunted than after TRH. These data suggest that the responsiveness of plasma prolactin to vasoactive intestinal polypeptide is defective in these patients, though the mechanism(s) are yet to be defined.     

Effect of mammalian thyrotropin releasing hormone on prolactin secretion by bullfrog adenohypophyses in vitro.

The effects of the mammalian thyrotropin-releasing hormone (TRH) on the secretion of prolactin by bullfrog adenohypophysis in vitro were investigated in short-term incubation and 24-hr organ culture experiments. Prolactin in the medium or in the incubated tissue was measured by either polyacrylamide disc gel electrophoresis and densitometry or by a homologous radioimmunoassay. The TRH was consistently effective in promoting prolactin release in vitro in concentrations of 10 ng/ml to 10 μg/ml. The tripeptide also caused an increase in the tissue prolactin content over a wide range of concentrations. These results indicate that TRH may function as a prolactin-releasing factor in the bullfrog.     

Nocturnal prolactin pulses in relation to luteinizing hormone and thyrotropin.

The two hypothalamic releasing factors, luteinizing hormone releasing hormone (LHRH) and thyrotropin releasing hormone (TRH), have been shown to stimulate pituitary prolactin (PRL) release as well as their respective pituitary hormones, luteinizing hormone (LH) and thyrotropin (TSH). In this study the influence of LH and TSH regulatory mechanisms on nocturnal PRL secretion was investigated by evaluating whether the coincidence of PRL with LH and TSH pulses occurred more frequently than would be expected if the hormone generators were not coupled. Thirty night studies were conducted in twelve healthy male subjects. Six subjects underwent 3 studies and 6 subjects 2 studies. Blood was collected into aliquots at 10 min intervals throughout the night and plasma concentrations of PRL, TSH, and LH were determined. From the plasma profiles, hormone secretory rates were calculated using a method of deconvolution. Significant plasma and secretory hormone pulses were identified by a peak detection computer program. For statistical analysis the night studies of each subject were concatenated. Concomitance between the plasma pulses of both TSH and LH with PRL was insufficient to reject the null hypothesis of random coincidence. An increase in the number of subjects demonstrating significant coincidence between the hormone pulses was obtained when secretory pulses were analysed. Seven of the 12 and 10 of the 12 subjects showed significant concomitance between PRL and respectively TSH and LH. This proportion was sufficient to confirm copulsatility between PRL and LH. These results suggest that LH regulatory mechanisms are involved in the generation of the nocturnal pulsatile PRL profile, TRH may also play a role in the secretion of PRL at a central level, but was not reflected in the plasma or secretory profiles because of other overriding regulatory factors.     

Disparity of thyrotropin (TSH) and prolactin responses to TSH-releasing hormone in obesity

The effect of TRH administration on TSH and PRL release was investigated in 11 obese women and 16 normal weight women. There were no differences in basal serum levels of estradiol, T3, T4, TSH, or PRL between the 2 groups. The increment of TSH levels in the obese group [mean maximum change (delta max), 19.3 +/- 3.0 (+/-SEM) mIU/liter] was significantly higher (P less than 0.025) than that in the control group (delta max, 11.3 +/- 1.3 mIU/liter), whereas PRL levels rose significantly less (P less than 0.025) in these obese women than in the control group (delta max, 738 +/- 132 and 1311 +/- 133 mIU/liter, respectively). Since serotonin is known to stimulate PRL and inhibit TSH release, deficiency of serotonin has been hypothesized as the cause of this disparity between TSH and PRL levels in obesity.     

Luteinizing hormone pulsatile secretion and pituitary response to gonadotropin releasing hormone and to thyrotropin releasing hormone in male epileptic subjects on chronic phenobarbital treatment

Endocrine changes have been reported in treated epileptic subjects, who often exhibit sexual dysfunctions, but the endocrine effects of single antiepileptic drugs have not been completely elucidated. In this study we have investigated the influence of phenobarbital (PB) on adenopituitary function and on peripheral sexual steroid pattern in 8 epileptic males. Chronic PB treatment does not modify luteinizing hormone (LH) pulsatile secretion. In the same subjects, LH and follicle stimulating hormone (FSH) response to Gonadotropin Releasing Hormone was blunted with respect to healthy controls both in terms of absolute values and of secretion areas. No difference was found in prolactin (PRL) response to Thyrotropin Releasing Hormone. In the epileptic group a significant increase in the levels of sex hormone binding globulin and a consequent decrease of the percent free testosterone have been observed. PB treatment also significantly lowers 17-beta-estradiol mean levels. These data suggest that PB independently affects both gonadotropin secretion and peripheral steroid pattern.     

Pituitary-thyroid hormone economy in healthy aging men: basal indices of thyroid function and thyrotropin responses to constant infusions of thyrotropin releasing hormone

In order to assess the effects of aging, as distinct from those of thyroid disease or extrathyroidal illness, on certain indices of thyroid function, we studied 74 healthy, ambulatory men recruited from the Baltimore Longitudinal Study on Aging. We determined basal serum values of T4, T3, rT3, thyroxine-binding globulin (TBG), and T3 resin uptake (T3RU) and calculated the free T4 index (FT4I = T4 X T3RU/100), free T3 index (FT3I = T3 X T3RU/100), and T4/TBG ratio for each subject. We used an ultrasensitive RIA to measure variations in basal concentrations of TSH within the normal range. We then infused TRH at a constant rate (0.4 microgram/min iv) for 240 min into 63 of the same men; serum samples, collected at 15-min intervals during the infusion, were analyzed for TSH by routine RIA. Subjects were divided into 3 groups according to age; A (n = 26, mean age = 39.4), B (n = 23, mean age = 60.0), and C (n = 25, mean age = 79.6). Analysis of variance with Duncan's multiple range test and regression analysis were used to evaluate data. There was no significant (P greater than 0.05) variation with age of basal serum values of T4, TBG, or T3RU. Comparison of groups A and C showed significant decreases of mean values of serum T3 (-11%, P less than 0.05), FT3I (-13%, P = 0.02), FT4I (-11%, P less than 0.01), and T4/TBG ratio (-12%, P less than 0.01) and an increase in serum TSH (+38%, P less than 0.05). For these variables, the mean values for group B were intermediate between, but not significantly different from, those of A and C. Regression analysis showed significant correlations of age with T3, FT3I, FT4I, T4/TBG, and TSH at P levels similar to those obtained by Duncan's test. No elderly individual exhibited a baseline elevation of TSH (greater than 7 microU/ml) or depression of T4 (less than 5 micrograms/dl), suggesting that primary hypothyroidism was not present in our old group. The basal TSH concentration did not correlate significantly with any index of thyroid function except with FT3I in group C (r = -0.43, P less than 0.05). In all age groups the TSH responses to TRH exhibited a biphasic pattern with early and late peaks.(ABSTRACT TRUNCATED AT 400 WORDS)     

Gender-biased activity of the novel prolactin releasing peptides: comparison with thyrotropin releasing hormone reveals only pharmacologic effects

The prolactin- (PRL) releasing activities of the newly described PRL-releasing peptides (PrRPs) were compared to that of thyrotropin-releasing hormone (TRH) in dispersed, rat anterior pituitary cell cultures. A dose-related stimulation of PRL release by TRH was observed in cells harvested from both intact male and random cycle female pituitary donors. The minimum effective dose of TRH ranged from 1 to 10 nM. Neither PrRP-20 nor PrRP-31 significantly altered PRL secretion in cells from male donors even at doses as high as 1 microM. In cells harvested from females, only the highest doses of PrRP-20 and PrRP-31 tested (0.1 and 1.0 microM) significantly stimulated PRL secretion. The PRL-releasing action of TRH was observed already at 15 min of incubation, whereas those of PrRP-20 and PrRP-31 appeared only after 1 and 2 h of incubation, and the magnitude of PRL release in the presence of 1 microM PrRPs was significantly less than that of a similar dose of TRH. These data do not suggest a physiologically relevant role for the PrRPs in the neuroendocrine regulation of PRL secretion in intact male and nonlactating, random-cycle female rats.     

Effect of gestational mastectomy on postpartum gonadotropin releasing hormone and thyrotropin releasing hormone-induced luteinizing hormone and prolactin response in first lactation Holstein cattle

First lactation Holstein cows were divided into two treatment groups to evaluate thyrotropin releasing hormone (TRH, 0.25 microgram/kg body weight) and gonadotropin releasing hormone (GnRH; 200 micrograms) induced secretion of prolactin (PRL) and luteinizing hormone (LH) on days 7 and 16 postpartum. Disregarding treatment, LH response was greater (p less than 0.01) on day 16 than day 7 postpartum (7.5 +/- 0.3 ng/ml on day 7 vs 10.2 +/- 0.3 ng/ml serum on day 16). Mastectomized cattle had similar time for initiation of LH increase, but peak concentrations were achieved later. Peak PRL concentrations were reached 12 to 15 min after injection and returned to baseline within 2.5 h in both groups. However, intact cows had higher (p less than 0.01) mean serum PRL than the mastectomized cows for 1 h following injection. Peak PRL concentration was 83.3 +/- 17.6 ng/ml for mastectomized cows vs 128.0 +/- 24.7 ng/ml for intact cows. It appears that udder removal allows for greater pituitary responsiveness to GnRH but diminishes PRL response to TRH suggesting the mammary gland differentially affects pituitary secretion of LH and PRL.     

Release of luteinizing hormone releasing hormone and thyrotropin releasing hormone from a synaptosome-enriched fraction of hypothalamic homogenates.

A mitochondrial fraction prepared from homogenates of rat hypothalamic tissue was found by means of electron microscopy to be enriched with synaptosomes. The release of luteinizing hormone releasing hormone (LHRH) and thyrotropin releasing hormone (TRH) from this preparation was investigated. After incubation, the synaptosomes were re-isolated by ultrafiltration; and the concentration of LHRH and TRH in the ultrafiltrate was determined by radioimmunoassay. When the synaptosome-enriched preparation was incubated in 0.32M sucrose at 1 or 30 C, less than 10% of the total LHRH and TRH was recovered in the ultrafiltrate. The two hormones were released by depolarizing concentrations (60 mM) of K+ in a Ca++-dependent manner, and the stimulatory effect of K+ was essentially complete within 2 min. In the presence of 2 mM Ca++, the release of LHRH and TRH increased with increasing K+ concentrations in the range 30-120 mM. Prostaglandin E2 (PGE2), PGF2 alpha, and PGF2 beta had little if any effect on LHRH or TRH release. When the synaptosome-enriched fraction was incubated in Hanks' balanced salt solution, the release of LHRH and TRH was about 10 times greater than that seen in 0.32M sucrose. It is concluded that a synaptosome-enriched fraction from the hypothalamus contains readily releasable pools of LHRH and TRH which are mobilized rapidly by depolarizing concentrations of K+ in a Ca++-dependent manner.