Prolactin and cyclosporine modulate adenosine transporters and adenosine A1 receptors in the rat brain

The existence of adenosine A1 receptors and adenosine transporters in the central nervous system has been well demonstrated, although their possible modulation by hormones and/or exogenous drugs is poorly understood. To further analyze these modulatory mechanisms, the effects of prolactin and cyclosporine (CyA) on adenosine A1 receptors and transporters were analyzed in the central nervous system. For this purpose the number and affinity of adenosine A1 receptors were measured using the specific antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) and the transporters with the high affinity ligand nitrobenzylthioinosine (NBTI). This procedure was carried out in hyperprolactinemic and control male rats treated with CyA or its vehicle for 8 days. As expected, pituitary grafting increased plasma prolactin levels (p<0.01). CyA treatment reduced but did not normalize (p<0.05) this parameter in hyperprolactinemic rats and did not modify circulating prolactin in control animals. Both hyperprolactinemia and CyA treatment reduced the number of adenosine transporters by 70% and by 40% the number of A1 receptors. The Kd for transporters was also reduced in all experimental groups. Hyperprolactinemia increased the affinity of A1 receptors (p<0.01) and CyA treatment did not further modify this parameter. These data demonstrated that prolactin and CyA influence adenosine transporters and A1 receptors at the central nervous system and suggest the existence of an interaction between prolactin and CyA may be operating to modulate these processes.     

Differential effects of bromocriptine treatment on LH release and copulatory behavior in hyperprolactinemic male rats

Hyperprolactinemia (hyperPRL) induced by grafting four pituitary glands under the kidney capsule suppresses copulatory behavior in male rats and sexually naive male mice. In mice sexual experience attenuates the suppressive effects of hyperPRL on mating behavior, thus a comparison of the behavioral consequences of inducing hyperPRL in sexually naive and experienced male rats was undertaken. Hyperprolactinemia had a significant suppressive effect on mating behavior in both groups of animals. Experienced animals showed deficits in all parameters studied except mount frequency and postejaculatory interval, while naive animals differed from respective controls only in mount latency, intromission latency, and intromission frequency. To determine if the inhibition of chronically elevated prolactin (PRL) levels would reverse the suppression of gonadotropin secretion and copulatory behavior in hyperprolactinemic animals, the effects of bromocriptine (CB-154) administration on plasma hormone levels and mating behavior were examined in pituitary-grafted and control rats. Bromocriptine treatment (1 mg/day for 14 days) led to increases in sexual activity in both the sham-operated and grafted animals. In the grafted animals, plasma PRL was reduced and plasma LH significantly increased in the CB-154-treated animals when compared to oil-treated controls. In sham-operated animals, CB-154 produced no significant changes in plasma LH or FSH despite the suppressed PRL levels. These results indicate that (1) hyperPRL induced by pituitary grafts can cause deficits in mating behavior in male rats despite previous sexual experience, and (2) while CB-154 may be acting through other mechanisms to stimulate copulatory behavior, the reduction of chronically elevated PRL levels due to CB-154 treatment is responsible for reversal of the suppressive effects of hyperPRL on LH secretion.     

High-calcium diet modulates effects of long-term prolactin exposure on the cortical bone calcium content in ovariectomized rats

High physiological prolactin induced positive calcium balance by stimulating intestinal calcium absorption, reducing renal calcium excretion, and increasing bone calcium deposition in female rats. Although prolactin-induced increase in trabecular bone calcium deposition was absent after ovariectomy, its effects on cortical bones were still controversial. The present investigation, therefore, aimed to study the effect of in vivo long-term high physiological prolactin induced by either anterior pituitary (AP) transplantation or 2.5 mg/kg prolactin injection on cortical bones in ovariectomized rats. Since the presence of prolactin receptors (PRLR) in different bones of normal adult rats has not been reported, we first determined mRNA expression of both short- and long-form PRLRs at the cortical sites (tibia and femur) and trabecular sites (calvaria and vertebrae) by using the RT-PCR. Our results showed the mRNA expression of both PRLR isoforms with predominant long form at all sites. However, high prolactin levels induced by AP transplantation in normal rats did not have any effect on the femoral bone mineral density or bone mineral content. By using (45)Ca kinetic study, 2.5 mg/kg prolactin did not alter bone formation, bone resorption, calcium deposition, and total calcium content in tibia and femur of adult ovariectomized rats. AP transplantation also had no effect on the cortical total calcium content in adult ovariectomized rats. Because previous work showed that the effects of prolactin were age dependent and could be modulated by high-calcium diet, interactions between prolactin and these two parameters were investigated. The results demonstrated that 2.0% wt/wt high-calcium diet significantly increased the tibial total calcium content in 9-wk-old young AP-grafted ovariectomized rats but decreased the tibial total calcium content in 22-wk-old adult rats. As for the vertebrae, the total calcium contents in both young and adult rats were not changed by high-calcium diet. The present results thus indicated that the adult cortical bones were potentially direct targets of prolactin. Moreover, the effects of high physiological prolactin on cortical bones were age dependent and were observed only under the modulation of high-calcium diet condition.     

Prolactin lowering effect of amphetamine in normoprolactinemic subjects and in physiological and pathological hyperprolactinemia

The effect on plasma prolactin (PRL) of d-amphetamine (Amph) was studied in normo- and hyperprolactinemic subjects. In normoprolactinemic women Amph failed to lower plasma PRL levels when infused intravenously over 1 h at the dose of 7.5 mg, but induced at the dose of 15.0 mg a modest inhibition of plasma PRL (maximum PRL inhibition 20 +/- 4.5% at 45 min). Likewise, in puerperal women Amph at the dose of 7.5 mg did not decrease significantly plasma PRL levels but it was active in this respect (maximum inhibition 37 +/- 10% at 120 min) at the dose of 15.0 mg. In subjects with presumptive evidence of a PRL-secreting adenoma, Amph at either the 7.5 mg or the 15.0 mg dose failed to alter baseline PRL levels. These results indicate that Amph is a poor PRL suppressor in either normo- or hyperprolactinemic subjects. It is proposed that this may be due to the drug's ability to effect release of dopamine mainly from a non-granular pool of the amine.     

The effects of prolactin on rat ovarian function

Hyperprolactinemia has been associated with several reproductive disorders. To investigate whether hyperprolactinemia directly affects rat ovarian function, we examined the ovarian histopathology and the activities of the four ovarian enzymes 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), 17-hydroxylase (17-OH), 17,20-desmolase (17,20-D) and aromatase in hyperprolactinemic rats and controls. Hypophysectomized, gonadotropin-treated Fisher rats were made hyperprolactinemic by isografting pituitary glands under the kidney capsule. The control animals received skeletal muscle. The ovaries were resected, pooled according to prolactin levels and microsomal enzyme activities were measured from each pool. Prolactin (PRL) levels were 344 +/- 23 ng/ml in the hyperprolactinemic rats and 18 +/- 5 ng/ml in the controls (p less than 0.001). Estradiol concentrations were 609 +/- 47 pg/ml in the hyperprolactinemic animals and 56 +/- 13 pg/ml in the controls (p less than 0.001). Ovarian and uterine weights were significantly higher in the hyperprolactinemic rats (p less than 0.02). Ovarian histopathology demonstrated benign polycystic transformation in the hyperprolactinemic animals. Hyperprolactinemia had no effect on 3 beta-HSD, but was associated with significant decreases in the 17-OH, 17,20-D and aromatase activities when compared to controls (p less than 0.001). We conclude that prolactin has a direct effect on rat ovarian function which appears to be independent of changes in gonadotropin secretion.     

Disturbed prolactin responses to dopamine-related substances in patients with acromegaly and hyperprolactinemia

We undertook this study, because conflicting data were reported about the dopaminergic regulation of prolactin (PRL) secretion in patients with acromegaly and hyperprolactinemia. In order to clarify the dopaminergic regulation of PRL secretion in patients with acromegaly and hyperprolactinemia, the effects of nomifensine, a central dopamine agonist, FK 33-824, a centrally antidopaminergically acting agent, and domperidone, a peripheral dopamine antagonist, on plasma PRL in these patients were studied. The results were compared with those observed in normal subjects and hyperprolactinemic patients, with or without a pituitary tumor. Nomifensine did not lower the PRL levels and FK 33-824 did not raise the PRL levels in acromegalic patients. In hyperprolactinemic patients, nomifensine did not lower the PRL levels and FK 33-824 failed to raise the PRL levels. Domperidone did not increase PRL in about a third of acromegalic patients, while TRH increased PRL in the all normoprolactinemic acromegalic patients. These results suggest that in acromegalic patients there may be a disturbance in dopamine related neurotransmission and that such disorders also seem to be present in patients with hyperprolactinemia, with or without a pituitary tumor.     

Deterioration of male sexual behavior in rats by the new prolactin-secreting tumor 7315b

The effects of hyperprolactinemia on male copulatory behavior in adult male and female rats were studied. Hyperprolactinemia was induced by the transplantable purely prolactin-secreting tumor 7315b. Male rats were castrated and received testosterone-filled capsules of different sizes which induced normal and subnormal testosterone levels. After sexual training the rats of the experimental groups were inoculated with tumor 7315b. Three weeks after tumor-inoculation high prolactin levels (2000-30000 ng/ml) were found. During this hyperprolactinemia ejaculation latency increased significantly, while the mount frequency and intromission frequency remained unchanged. Only 9 out of 22 rats ejaculated 19 days after inoculation. Moreover, it appeared that the inhibitory effect of the tumor was as strong in the presence of normal (2.33 +/- 0.07 ng/ml) as in the presence of low (0.35 +/- 0.01 ng/ml) testosterone levels. The inhibitory effect of tumor 7315b on copulatory behavior was not influenced by adrenalectomy. In gonadectomized female rats bearing testosterone-filled capsules tumor 7315b induced prolactin levels of about 2000 ng/ml and an almost complete cessation of mounts and intromission patterns 4 weeks after tumor-inoculation. It was concluded that tumor 7315b causes a strong inhibitory effect on male copulatory behavior in male and female rats and that this effect is not influenced by the presence of normal or low testosterone levels or removal of the adrenals, suggesting a direct effect of prolactin on brain functions.     

Effects of hyperprolactinemia on prolactin and LH pulsatile pattern in female rats.

Prolactin (PRL) and luteinizing hormone (LH) secretions are very closely-related. To further understand these mechanisms, the pulsatile secretion pattern of both hormones in experimentally-induced hyperprolactinemia has been studied in adult female rats. Hyperprolactinemia was induced by the transplanting of two pituitary glands. Nine days after the transplant operation, rats were bled (75 or 100 microliters/7 min for 3 h). Serum samples were analyzed for prolactin and LH values by RIA. Hyperprolactinemia modifies pulsatile PRL secretion by increasing the absolute amplitude and duration of the peaks together with a decrease in their frequency. Also, the mean values of the hormone during the whole studied period were increased. Hyperprolactinemia was followed by an increase in the mean values of LH and in the absolute amplitude of the peaks. All these results suggest that hyperprolactinemia induced by pituitary grafting in adult female rats, is followed by a significant change in prolactin and LH pulsatility, which may explain, to some extent, the effects of hyperprolactinemia on reproduction.     

Progesterone administration prolongs the inhibitory effects of hyperprolactinemia on luteinizing hormone secretion in acutely ovariectomized rats

Several studies have shown that hyperprolactinemia in rats inhibits the post-gonadectomy rise in plasma luteinizing hormone (LH) for a limited period only. In intact rats the suppression of plasma LH during hyperprolactinemia is more prolonged. In the present study we have examined the possibility that the elevated levels of progesterone brought about by the raised plasma prolactin levels in intact rats are involved in the maintenance of LH inhibition. We have observed the effect of exogenous progesterone administration during the early post-ovariectomy period on plasma LH levels in female rats made hyperprolactinemic by administration of the dopamine antagonist, domperidone. Following ovariectomy of virgin, female rats, plasma LH was determined on each day from Day 3 to Day 10 after ovariectomy. In control rats plasma LH had increased by approximately 5-fold during the period of the experiment. In control rats treated with progesterone the rise in plasma LH was inhibited temporarily but LH had increased to similar levels to the controls by Day 10. In hyperprolactinemic rats LH was suppressed until Day 7, after which significant rises were observed. However, in hyperprolactinemic rats treated with progesterone, LH did not rise in a similar fashion, and remained low throughout the experiment. We conclude that a combination of hyperprolactinemia and raised plasma progesterone concentrations is necessary for the continued inhibition of LH release after ovariectomy.     

Daily Changes of GABA and Taurine Concentrations in Various Hypothalamic Areas Are Affected by Chronic Hyperprolactinemia

This study was designed to characterize, in anterior, mediobasal, and posterior hypothalamic and median eminence, the 24h changes of gamma aminobutyric acid (GABA) and taurine (TAU) contents in adult male rats and to analyze whether chronic hyperprolactinemia may affect these patterns. Rats were turned hyperprolactinemic by a pituitary graft. Plasma prolactin (PRL) levels increased after pituitary grafting at all time points examined. A disruption of the circadian rhythm was observed in pituitary-grafted rats, whereas GABA and TAU content followed daily rhythms in all areas studied in controls. In the mediobasal hypothalamus, two peaks for each amino acid were found at midnight and midday. In the anterior hypothalamus, GABA and TAU showed only one peak of concentration at midnight. In the posterior hypothalamus, the values of both GABA and TAU were higher during the light as compared to the dark phase of the photoperiod. In the median eminence GABA content peaked at 20:00h, the time when TAU exhibited the lowest values. Hyperprolactinemia abolished the 24h changes of GABA in the mediobasal hypothalamus and reduced its content as compared to controls. Hyperprolactinemia advanced the diurnal peak of TAU to 12:00h in the mediobasal hypothalamus and did not modify the 24:00h peak. In the anterior hypothalamus, hyperprolactinemia increased GABA and TAU contents during the light phase while it decreased them during the dark phase of the photoperiod. In the posterior hypothalamus hyperprolactinemia did not modify GABA or TAU patterns as compared to controls. In the median eminence hyperprolactinemia increased the 20:00h peak of GABA and shift advanced the decrease in TAU content at 20:00h and its maximum at 24:00h as compared to controls. These data show that GABA and TAU content exhibit specific daily patterns in each hypothalamic region studied. PRL differentially affects the daily pattern of these amino acids in each hypothalamic region analyzed.     

Daily changes of GABA and taurine concentrations in various hypothalamic areas are affected by chronic hyperprolactinemia

This study was designed to characterize, in anterior, mediobasal, and posterior hypothalamic and median eminence, the 24h changes of gamma aminobutyric acid (GABA) and taurine (TAU) contents in adult male rats and to analyze whether chronic hyperprolactinemia may affect these patterns. Rats were turned hyperprolactinemic by a pituitary graft. Plasma prolactin (PRL) levels increased after pituitary grafting at all time points examined. A disruption of the circadian rhythm was observed in pituitary-grafted rats, whereas GABA and TAU content followed daily rhythms in all areas studied in controls. In the mediobasal hypothalamus, two peaks for each amino acid were found at midnight and midday. In the anterior hypothalamus, GABA and TAU showed only one peak of concentration at midnight. In the posterior hypothalamus, the values of both GABA and TAU were higher during the light as compared to the dark phase of the photoperiod. In the median eminence GABA content peaked at 20:00h, the time when TAU exhibited the lowest values. Hyperprolactinemia abolished the 24h changes of GABA in the mediobasal hypothalamus and reduced its content as compared to controls. Hyperprolactinemia advanced the diurnal peak of TAU to 12:00h in the mediobasal hypothalamus and did not modify the 24:00h peak. In the anterior hypothalamus, hyperprolactinemia increased GABA and TAU contents during the light phase while it decreased them during the dark phase of the photoperiod. In the posterior hypothalamus hyperprolactinemia did not modify GABA or TAU patterns as compared to controls. In the median eminence hyperprolactinemia increased the 20:00h peak of GABA and shift advanced the decrease in TAU content at 20:00h and its maximum at 24:00h as compared to controls. These data show that GABA and TAU content exhibit specific daily patterns in each hypothalamic region studied. PRL differentially affects the daily pattern of these amino acids in each hypothalamic region analyzed.     

Changes in substance P content at the hypothalamic-pituitary axis during the Wallerian degeneration of peripheral sympathetic neurons after superior cervical ganglionectomy in male rats: effect of hyperprolactinemia

The effects of Wallerian degeneration of the peripheral sympathetic neurons projecting to the hypothalamus on the mechanism of interaction between prolactin and substance P (SP) were examined. The effects of superior cervical ganglionectomy (SCGx) on SP content in various hypothalamic regions and in the hypophysis were evaluated in control and hyperprolactinemic rats. Male rats that received pituitary transplants at the age of 5 days and age-matched sham-operated controls were used. Pituitary grafting significantly increased circulating values of prolactin, as did SCGx. In hyperprolactinemic rats, SCGx partially decreased plasma prolactin levels. Neonatal hyperprolactinemia decreased SP content in the anterior (AH) and posterior (PH) hypothalamus and in the median eminence (ME), but increased it in the mediobasal hypothalamus (MBH). Acute SCGx significantly increased SP in the MBH, PH, and ME. SCGx in hyperprolactinemic animals further increased SP content in MBH. In the ME and Ah, SCGx in pituitary grafted rats decreased SP content as compared with the controls. In the pituitary gland (PG), SCGx only decreased SP content in hyperprolactinemic, but not in control rats. An interaction between peripheral nor-adrenergic neurons and prolactin to regulate SP within the hypothalamus was positive in the MBH, AH, ME, and PG, but not in the PH. These data indicate the existence of interactive mechanisms between prolactin and the peripheral sympathetic neurons to regulate SP content at the hypothalamic-pituitary axis. Interrelationships between prolactin and SP were also observed.     

A mild magnesium deprivation affects calcium excretion but not bone strength and shape, including changes induced by nickel deprivation, in the rat

An experiment was performed to determine the effect of a mild magnesium deprivation on calcium metabolism and bone composition, shape, and strength in rats, and whether nickel deprivation exacerbated or alleviated any changes caused by the magnesium deprivation. Weanling male rats were assigned to groups of 10 in a factorial arrangement, with variables being supplemental nickel at 0 and 1 mg/kg and magnesium at 250 and 500 mg/kg of diet. The basal diet contained about 30 ng Ni/g. Urine was collected for 24 h during wk 8 and 12, and rats were euthanized 13 wk after dietary treatments began. Mild magnesium deprivation decreased the urinary excretion of calcium and increased the tibia concentration of calcium but did not affect femur shape or strength (measured by a three-point bending test). Dietary nickel did not alter these effects of magnesium deficiency. Nickel deprivation increased the urinary excretion of phosphorus and the femur strength variables maximum force and moment of inertia. Strength differences might have been the result of changes in bone shape. Magnesium deprivation did not alter the effects of nickel deprivation on bone. The findings indicate that a mild magnesium deficiency affects calcium metabolism but that this does not markedly affect bone strength or shape, and these effects are not modified by dietary nickel. Also, nickel deprivation affects phosphorus metabolism and bone strength and shape; these effects apparently are not caused by changes in magnesium metabolism or utilization.     

Diagnostic value of thyrotropin releasing hormone test in 129 patients with suspected tumoral hyperprolactinemia

In 129 hyperprolactinemic (PRL > or = 100 ng/mL) and 100 normoprolactinemic patients (PRL 0-25 ng/mL), delta max. PRL (the difference between maximal prolactin (PRL) after thyrotropin releasing hormone (TRH) injection and basal value) was compared with basal PRL and computed tomography (CT) of the sellar region. In 122 hyperprolactinemic patients delta max. PRL was < 100%, while tumor was found in 106 of them. In the remainder seven hyperprolactinemic patients delta max. PRL was > or = 100% and CT showed no tumor. A significant difference in delta max. PRL between hyperprolactinemic patients without and those with verified adenoma was found and showed a significant negative correlation with basal PRL. Between 122 hyperprolactinemic patients with delta max. PRL < 100%, mean basal PRL and duration of clinical symptoms were significantly lower in 16 patients with normal CT compared to 106 patients with tumor. All normoprolactinemic patients showed delta max. PRL > or = 100% and no tumor on CT. PRL stimulation disturbance precedes tumor visualization and represents a decisive diagnostic parameter in hyperprolactinemic patients with no tumor signs.     

Rat hepatic prolactin receptor: pubertal exposure to sex steroids alters responsivity to testosterone

Administration of testosterone enanthate to adult female rats lowered the level of hepatic prolactin receptor. Pubertal exposure of intact female rats to testosterone enanthate at the dose used did not affect the level of hepatic prolactin receptor in adults. However, the responsivity of such treated rats to testosterone challenge in adulthood was enhanced. Prepubertal ovariectomy of female rats lowered the level of hepatic prolactin receptor in adulthood. Exposure of the ovariectomized rats during puberty to mestranol (ethynylestradiol 3-methyl ether) at the dose used did not restore the normal adult female rat's level of hepatic prolactin receptor. However, they did become more resistant to subsequent testosterone challenge in adulthood. Exposure of prepubescent ovariectomized rats to testosterone enanthate during puberty reduced the already diminished level of hepatic prolactin receptor further. In addition, these rats were rendered more responsive to testosterone challenge in adulthood.     

The effect of luteinizing hormone releasing hormone on the copulatory behavior of hyperprolactinemic male rats

The present study was undertaken to test the hypothesis that the deficits in copulatory behavior observed in hyperprolactinemic male rats may be related to a reduction in hypothalamic release of luteinizing hormone releasing hormone (LHRH). Adult male Fischer 344 rats were made hyperprolactinemic by ectopic pituitary grafts or were sham operated and 30 min prior to being tested for copulatory performance received a single subcutaneous injection of 500 ng LHRH, 100 ng LHRH, or saline. On different occasions, testosterone (T) levels were measured in plasma collected 30 min following identical treatments. Plasma prolactin (PRL) levels were determined in samples collected 30 min after injection of 500 ng LHRH. Pituitary grafting produced the expected, significant increase in plasma PRL levels and significant deficits in copulatory behavior. Treatment of hyperprolactinemic subjects with 500 ng LHRH significantly reduced both the time to first intromission and the time to ejaculation to times comparable with those of sham-operated subjects. The 100-ng dose produced a significant reduction in mount frequency. Plasma T levels were significantly elevated following either dose of LHRH. These results demonstrate that exogenous LHRH can restore normal copulatory performance in hyperprolactinemic male rats and support the hypothesis that a reduction in hypothalamic LHRH release is responsible for the behavioral deficits observed in those animals.     

Inflammation causes tissue-specific depletion of vitamin B<Subscript>6</Subscript>

Previously we observed strong and consistent associations between vitamin B₆ status and several indicators of inflammation in patients with rheumatoid arthritis. Clinical indicators, including the disability score, the length of morning stiffness, and the degree of pain, and biochemical markers, including the erythrocyte sedimentation rate and C-reactive protein levels, were found to be inversely correlated with circulating vitamin B₆ levels. Such strong associations imply that impaired vitamin B₆ status in these patients results from inflammation. In the present study we examined whether inflammation directly alters vitamin B₆ tissue contents and its excretion in vivo. A cross-sectional case-controlled human clinical trial was performed in parallel with experiments in an animal model of inflammation. Plasma and erythrocyte and pyridoxal 5'-phosphate concentrations, urinary 4-pyridoxic acid excretion, and the activity coefficient of erythrocyte aspartate aminotransferase were compared between patients and healthy subjects. Adjuvant arthritis was induced in rats for investigating hepatic and muscle contents as well as the urinary excretion of vitamin B₆ during acute and chronic inflammation. Patients with rheumatoid arthritis had low plasma pyridoxal 5'-phosphate compared with healthy control subjects, but normal erythrocyte pyridoxal 5'-phosphate and urinary 4-pyridoxic acid excretion. Adjuvant arthritis in rats did not affect 4-pyridoxic acid excretion or muscle storage of pyridoxal 5'-phosphate, but it resulted in significantly lower pyridoxal 5'-phosphate levels in circulation and in liver during inflammation. Inflammation induced a tissue-specific depletion of vitamin B₆. The low plasma pyridoxal 5'-phosphate levels seen in inflammation are unlikely to be due to insufficient intake or excessive vitamin B₆ excretion. Possible causes of decreased levels of vitamin B₆ are discussed.     

Effects of elevated prolactin and its normalization on thyroid hormone, cardiac beta-adrenoreceptor number and beta-adrenergic responsiveness

Subcutaneous inoculation of the prolactin secreting MtTW15 adenoma in male Wistar Furth rats for 4 weeks produced a significant increase in serum prolactin and a corresponding decrease in peripheral beta-adrenergic responsiveness. Both the isoproterenol induced drink and heart rate responses used to assess the beta-adrenergic responsiveness were significantly reduced in the hyperprolactinemic rat. Serum T3 and T4 levels were measured as was cardiac beta-adrenergic receptor number to ascertain if an alteration of thyroid hormone and a resultant decrease in beta-adrenergic receptor number was responsible for the attenuated beta-adrenergic responsiveness. Serum T4 was significantly reduced in the hyperprolactinemic group (1.9 +/- 0.3 microgram%) as compared to the control group (6.4 +/- 0.l5 microgram%). However there was no significant difference in serum T3 or in cardiac beta-adrenergic receptor number between the two groups. Removal of the MtTW15 adenoma resulted in a normalization of serum prolactin, T4, and in the responsiveness of the peripheral beta-adrenergic system within 4-6 weeks. These results indicate that the attenuated beta-adrenergic responsiveness associated with hyperprolactinemia is reversible and not dependent on a reduction in beta-adrenergic receptor number.     

Endogenous prolactin modulated the calcium absorption in the jejunum of suckling rats

Prolactin has been reported to stimulate intestinal calcium absorption in young and mature, but not aging rats. The present study was performed on suckling rats to elucidate the actions of endogenous prolactin on calcium absorption in various intestinal segments. Before measuring the calcium fluxes, 9-day-old rats were administered for 7 days with 0.9% NaCl, s.c. (control), 3 mg/kg bromocriptine, i.p., twice daily to abolish secretion of endogenous prolactin, or bromocriptine plus exogenous 2.5 mg/kg prolactin, s.c. Thereafter, the 16-day-old rats were experimented upon by instilling the 45Ca-containing solution into the intestinal segments. The results showed that, under a physiological condition, the jejunum had the highest rate of calcium absorption compared with other segments (1.4 +/- 0.35 micromol.h-1.cm-1, p < 0.05). The duodenum and ileum also manifested calcium absorption, whereas the colon showed calcium secretion. Lack of endogenous prolactin decreased lumen-to-plasma and net calcium fluxes in jejunum from 2.07 +/- 0.31 to 1.19 +/- 0.12 and 1.40 +/- 0.35 to 0.88 +/- 0.18 micromol.h-1.cm-1 (p < 0.05), respectively, and exogenous prolactin restored the jejunal calcium absorption to the control value. Endogenous prolactin also had an effect on the duodenum but, in this case, exogenous prolactin did not reverse the effect of bromocriptine. However, neither ileal nor colonic calcium fluxes were influenced by prolactin. Because luminal sodium concentration has been demonstrated to affect calcium absorption in mature rats, the effect of varying luminal sodium concentrations on calcium fluxes in suckling rats was evaluated. The jejunum was used due to its highest rate of calcium absorption. After filling the jejunal segments with 124 (control), 80, 40 mmol/L Na+-containing or Na+-free solution, increases in calcium absorption were found to be inversely related to luminal sodium concentrations in both control and bromocriptine-treated rats. The plasma concentration of 45Ca under luminal sodium free condition was also higher than that of the control condition (2.26% +/- 0.07% vs. 2.01% +/- 0.09% administered dose, p < 0.05). However, 3H-mannitol, a marker of the widening of tight junction that was introduced into the lumen, had a stable level in the plasma during an increase in plasma 45Ca, suggesting that the widening of tight junction was not required for enhanced calcium absorption. In conclusion, calcium absorption in suckling rats was of the highest rate in the jejunum where endogenous prolactin modulated calcium absorption without increasing the paracellular transport of mannitol.