Prolactin Release In Male Rats Research Articles

Possible estrogenic and/or antiandrogenic effects of methoxychlor on prolactin release in male rats.

Methoxychlor (MTX) is a pesticide currently used as a substitute for dichloro-diphenyl-trichloroethane (DDT). This organochloride insecticide has some estrogenic properties, and may modify the feedback mechanisms of steroids on the hypothalamus and pituitary. This work was undertaken to explore the possible effects of MTX on the episodic prolactin release and to analyze whether these effects are mediated by dopamine (DA), luteinizing hormone (LH), and/or testosterone. Adult male Sprague-Dawley rats were administered 25 mg/kg/day of MTX in sesame oil for 30 days. Control animals received vehicle only. The episodic prolactin release and plasma testosterone levels were measured as well as the dopamine (DA) content in the median eminence (ME) and in the anterior (AH), mediobasal (MBH), and posterior (PH) hypothalamus. The mean serum prolactin levels and absolute pulse amplitude of the hormone increased after the xenobiotic administration, whereas its relative pulse amplitude diminished. The frequency and duration of prolactin peaks and its half-life were not modified by the treatment with the pesticide. On the other hand, methoxychlor decreased the DA content in ME, increased it in AH, and did not change it in MBH or PH. MTX decreased plasma levels of LH and testosterone compared with controls. These data suggest estrogenic and antiandrogenic effects of MTX on the episodic prolactin secretion; the changes observed in prolactin release could be explained, at least in part, by some of the changes of DA at the hypothalamus and of LH at the pituitary, but not by changes of testosterone at the testicular level.

Effect of Nω‐nitro‐l‐arginine methyl ester, a nitric oxide synthesis inhibitor, on stress‐ and morphine‐induced prolactin release in male rats

1. The effect of the nitric oxide synthesis inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) was investigated on stress- and morphine-induced prolactin (PRL) secretion in vivo in male rats, by use of a stress-free blood sampling and drug administration method by means of a permanent indwelling catheter in the right jugular vein. 2. Three doses of L-NAME were tested (1, 10 and 30 mg kg-1) and were given intraperitoneally one hour before blood sampling; control rats received saline. After the first blood sample, rats received an initial intravenous injection of morphine (3, 6 or 12 mg kg-1) or were subjected to immobilization stress. In the case of a morphine administration, rats received a second dose of morphine (3, 6 or 6 mg kg-1, respectively) 90 min later, when tolerance had developed, while rats subjected to immobilization stress received 6 mg kg-1 morphine 90 min after onset of stress. 3. L-NAME had no effect on basal plasma PRL concentration. However, it potentiated acute morphine-induced PRL secretion and attenuated the subsequent tolerance in a dose-dependent way. Immobilization stress-induced PRL secretion was inhibited dose-dependently by L-NAME, as was its subsequent tolerance to morphine; however, in this case, in a reversed dose-dependent way. 4. When the highest dose of morphine (12 mg kg-1) was combined with the highest dose of L-NAME pretreatment (30 mg kg-1), all rats showed a dramatic potentiation of the morphine-induced PRL rise compared to controls. Moreover, all of these rats died within 90 min after the administration of morphine. 5. These results show that NO plays a role in the acute opioid action on PRL release during stress as well as in the development of tolerance to the opioid effect, and some possible mechanisms are discussed.

Studies on the site of ethanol action in inducing prolactin release in male rats

Hypersecretion of prolactin (PRL) has been implicated as one of the factors that mediate ethanol-induced hypogonadism, but the site(s) is the central nervous system where ethanol acts to lead to the stimulation of PRL secretion is unknown. To clarify the site(s) of ethanol action, medial basal hypothalamic deafferentation (MBHD) or medial basal hypothalamic ablation (MBHA) were performed stereotaxically in male rats, and their PRL secretory capacity in response to acute ethanol administration was compared with that of intact or sham-operated controls. In intact control rats, plasma immunoreactive PRL concentration increased markedly ( P < .001 v saline injection) following ethanol 400 to 500 mg/100 g body weight (BW) intraperitoneally (IP). The PRL response was dose-related and reached a maximum plateau level at 15 minutes. Plasma PRL returned to a near-basal level by 60 minutes. The response was blocked completely ( P < .001) by pretreatment with dopamine (1 mg per rat), a specific inhibitor of adenohypophyseal PRL secretion. In sham-operated rats and in MBHD and MBHA rats, ethanol (500 mg/100 g BW IP) induced a significant ( P < .001 to .05) elevation of PRL relative to the respective saline treatment. The basal level was significantly ( P < .005) lower in the MBHD group (5.3 ± 0.9 ng/mL) and significantly ( P < .001) higher in the MBHA group (101.1 ± 15.7 ng/mL) than in the sham group (17.2 ± 5.9 ng/mL). These results suggest the following: (1) acute ethanol administration stimulates PRL secretion from the pituitary in a dose-related manner, (2) ethanol appears to have direct stimulatory effects on adenohypophyseal PRL secretion, and (3) extrahypothalamic brain areas exert a stimulatory influence and the hypothalamus an inhibitory influence on basal PRL secretion.

Opioid components of the clockwork that governs luteinizing hormone and prolactin release in male rats.

Daily rhythms of secretion have been described for luteinizing hormone (LH) and prolactin (PRL) from the anterior pituitary of rats. Using selective opioid antagonists, we found that mu and kappa opioid receptor ligands regulate LH and PRL secretion and, of particular interest, that the magnitude of opioidergic effects varies with the time of day. In addition, incomplete temporal overlapping of the LH and PRL responses to the antagonists suggests that different endogenous opioid pathways, with different temporal profiles of peptide release, may control each of these hormones.

Nipple development and pup-induced prolactin release in male rats treated prenatally with the antiandrogen flutamide

While maternal female rats display increases in circulating prolactin (PRL) concentrations in response to pup exposure, parental male rats fail to show such an increase. One possible explanation for the lack of an acute PRL response in parental male rats is that males do not have nipples and therefore do not receive stimuli from the pups comparable to those experienced by parental female rats. To examine the contribution of nipple presence and possible stimulation, i.e. suckling, in this sexually differentiated endocrine response, male rats were exposed from days 12–15 of gestation to the antiandrogen flutamide. As adults, flutamide-exposed males had nipples. These males and a group of control males were castrated in adulthood and treated with a 21-day hormone regimen (estradiol and progesterone) that effectively stimulates parental behavior in adult rats. Following hormone treatment, mammary tissue from one set of flutamide-treated males was examined histologically to assess nipple and mammary gland development and responsiveness of these tissues to hormonal stimulation. Additional sets of flutamide-treated and control animals were tested for parental behavior. These latter animals were implanted with indwelling atrial cannulae on day 4 of parental behavior and subsequently bled on day 6 in the absence of young and on day 8 after presentation of young. PRL concentrations did not change in either the flutamide-treated or control parental males bled in the presence or absence of young. These findings indicate that pup exposure itself is insufficient to induce an acute release of prolactin in parental male rats with nipples and suggest that additional pup-related sensory input and/or possibly a female-like central nervous system may be required to induce prolactin secretion in parental males.

Histamine sensitive sites in hippocampus: Their probable role on prolactin release in male rats

The effect of histamine (HA), 3-methyl-histamine (3MHA), HA antagonists or drugs interfering with HA synthesis, microinjected into the hippocampus (HPC), on prolactin (PRL) secretion were studied in rats. Three experiments were performed. In Experiment 1, increasing doses of HA or 3-MHA (9–90 nmol) were microinjected stereotaxically into the ventral HPC of adult male rats. In Experiment 2, 135 nmol of pyrilamine (PYR, an H1-HA-antagonist) or ranitidine (RAN, an H2-HA-antagonist) were administered locally into the ventral HPC. Fifteen min later, the rats were microinjected again with 45 nmol of HA. In Experiment 3, rats were microinjected with different doses of HA-antagonists or with 20 nmol of alpha-fluormethyl-histidine (FMH, an inhibitor of the enzyme of HA synthesis) and later subjected to an immobilization stress of 15 min duration. In all cases, the PRL plasma concentrations were measured in blood samples taken at different time intervals (0–120 min) after the last brain injection. Results showed that HA applied locally in ventral HPC induced an increase in PRL levels which was statistically significant from saline-injected rats between 5–30 min after the HPC stimulation. On the contrary, local applications of 3-MHA did not change significantly the PRL blood levels (Experiment 1). Only PYR did block partially the PRL response due to HA in basal conditions. RAN in these later conditions had no effect (Experiment 2). When animals were subjected to stress neither PYR nor RAN, alone or in combination, locally applied were able to block the PRL increase due to stress. Only FMH blunted significantly the hormone response. The present results suggest that HPC in some conditions may be affecting the PRL release through the participation of HA sensitive sites present in this limbic structure.

The putatively selective dopamine autoreceptor antagonists (+)-AJ 76 and (+)-UH 232 stimulate prolactin release in rats

The 2-aminotetralin derivatives cis-(+)-(1S,2R)-5-methoxy-1-methyl-2-(n-propylamino)tetralin, (+)-AJ 76, and cis-(+)-(1S,2R)-5-methoxy-1-methyl-2-(di-n-propylamino)tetralin, (+)-UH 232, are novel centrally acting stimulants with a putative action as selective dopamine (DA) autoreceptor antagonists. In the present study these compounds were evaluated with respect to their effects on prolactin release in male rats. Both (+)enantiomers caused a pronounced increase in plasma prolactin levels in previously untreated animals. The effects of (+)-AJ 76 and (+)-UH 232 were virtually similar, except for a higher initial increase after the latter compound. In agreement with earlier reports, the reserpine-induced elevation of plasma levels of prolactin was strongly suppressed by the DA autoreceptor agonist B-HT 920. This effect of B-HT 920 was completely blocked by (+)-AJ 76 and by (+)-UH 232, indicating that both (+)enantiomers antagonize lactotroph DA receptors. The present findings support the notion that lactotroph DA receptors resemble DA autoreceptors rather than postsynaptic DA receptors. A possible difference between the auto-/lactotroph vs. postsynaptic DA receptors with respect to both the responsiveness to agonists and to the affinity of pure antagonists is discussed.

Supression of basal and stress-induced prolactin release and stimulation of luteinizing hormone secretion by α-melanocyte-stimulating hormone

α-MSH and β-endorphin, both synthesized from a common precursor, have opposite behavioral actions. In order to determine if these peptides have opposite effects on pituitary function, basal LH secretion and basal and stress-induced prolactin release were studied in adult male rats after intraventricular injection of α-MSH. Each rat also received intraventricular saline in order to serve as its own control. 18 μg α-MSH stimulated plasma LH from 16.5 ± 2.5 (SEM) ng/ml to a peak of 27.2 ± 4.0 and 26.0 ± 4.9 n g/ml at 5 and 10 min, and suppressed prolactin from 3.5 ± 0.7 ng/ml to 1.3 ± 0.1 and 1.2 ± 0.1 ng/ml at 15 and 30 min. Intraventricular α-MSH also significantly blunted the prolactin rise associated with the stress of swimming. 10 and 20 min after the onset of swimming, prolactin levels in rats pretreated with α-MSH were significantly diminished: 7.4 ± 1.5 and 6.5 ± 2.0 ng/ml vs 23.8 ± 3.6 and 15.2 ± 2.8 after normal saline. Similarly, des-acetyl α-MSH which is the predominant form of α-MSH in the hypothalamus, diminished the stress-induced prolactin rise from 18.4 ± 5.3 and 11.2 ± 3.4 ng/ml at 10 and 20 min to 10.0 ± 2.4 and 5.5 ± 1.6 ng/ml. We conclude that centrally administered α-MSH stimulates LH and suppresses basal and stress-induced prolactin release in male rats. These actions are opposite to those previously shown for β-endorphin and suggest that α-MSH may antagonize the effects of β-endorphin on pituitary function.

Immediate prolactin release after pericommissural deafferentation in behaving male rats

Adult male rats received a chronic midline implant of Halász-type knife placed at the level of the anterior commissure. A chronically implanted heart cannula allowed for sequential blood sampling in unrestrained conditions. Anterior knife rotation of 180° induced a significant increase of plasma prolactin concentration in 30 min. Plasma LH levels remained within control levels. It is suggested that neural projections dorsally entering the preoptic-suprachiasmatic region are significantly involved in the control of prolactin release in male rats.

Inhibitton of prolactin release by stimulation of presynaptic serotonin autoreceptors

The effects of 5-methoxy-N, N-dimethyltryptamine (5-MeODMT), a serotonin agonist with a preferential action on presynaptic autoreceptors, on prolactin release in male rats was determined. Basal serum prolactin levels were not altered after administration of 1.0, 2.0, 5.0, 10.0 or 20.0 mg/kg of 5-MeODMT. Pretreatment with 5-MeODMT reduced prolactin release by agents that depend on serotonergic neurotransmission for part of their prolactin release stimulation. Prolactin release in response to L-5-hydroxytryptophan (5-HTP) or morphine was significantly reduced by pretreatment of the rats with 5-MeODMT. The results of this experiment indicate that 5-MeODMT act as a presynaptic serotonin autoreceptor stimulant and not as a postsynaptic serotonin agonist on the neuronal systems that control prolactin release.

Vasopressin has a direct effect on prolactin release in male rats.

Prolactin-releasing (PRF) activity was found in Pitressin (a commercial extract from posterior pituitary for vasopressin). Injection of Pitressin into conscious free-moving rats implanted with a permanent atrial indwelling cannula, produced a transient increase in prolactin concentration in the circulation. In order to find out whether the PRF activity was due to vasopressin or to an unidentified component in the Pitressin, we tested synthetic lysine vasopressin and demonstrated that vasopressin (1 U/kg) elevated plasma prolactin concentration about threefold. In contrast, oxytocin (1 U/kg) did not alter the prolactin concentration. In order to find out whether the effect of vasopressin is a direct or indirect action, we tested the vasopressin effect on hypophysectomized rats which had previously been implanted with 2 adenohypophyses under the kidney capsule. Again this dose (2 U/kg) of vasopressin elevated circulating plasma prolactin. These experiments indicate that vasopressin can elevate circulating prolactin concentration in nonestrogen-primed normal male rats and that vasopressin also stimulates prolactin secretion from transplanted glands dissociated from direct hypothalamic control.

Effect of 3-aminopropanesulfonic acid and allylglycine on prolactin release in male rats.

AbstractThe effect of the administration of a γ-aminobutyric acid (GABA) receptor agonist, 3-aminopropanesulfonic acid (3-APSA), and an inhibitor of the enzyme glutamic acid decarboxylase, allylglycine, on prolactin secretion was studied in castrated male rats. Serum prolactin levels were determined in basal conditions, after the injection of the drugs, and after the administration of sulpiride. The injection of 3-APSA did not significantly alter serum prolactin levels, but did decrease the release of prolactin after the administration of sulpiride. The injection of allylglycine increased the prolactin response to sulpiride. These data are consistent with the possibility that GABA may have an inhibitory influence on prolactin secretion.

Neural control of prolactin release in male rats: A possible inhibitory pericommissural component

Adult male rats under pentobarbital anesthesia received different types of “roof” knife cuts at the level of the anterior commissure. The cutting blade was 1.5 mm long and L-shape. Plasma prolactin concentrations were monitored every 30 min starting immediately before the lesion for a total period of 90 min. Mean prolactin values did not show significant changes in the following groups: no knife rotation, posterior rotation at a depth of 7.5 mm (subcommissural), and posterior rotation at a depth of 6.5 mm (supracommissural). On the other hand, anterior knife rotation at 6.5 mm (supracommissural) resulted in an immediate, significant increase in the plasma prolactin concentration 30 min after the lesion. Hormone concentrations were still high at 60 min. The results suggest the existence of significant projection components passing through and/or making synaptic contact at the level of the preoptic-suprachiasmatic region with elements involved in the (inhibitory) control of prolactin release in the male rat. These projections may take origin in the amygdala and/or hippocampus.

Inhibitory effects of substance P on the gamma-amino-butyric acid and gamma-hydroxybutyric acid-induced growth hormone and prolactin release in male rats

Gamma-aminobutyric acid (GABA) at 50 μg/10 μ1 was injected into the lateral ventricle after pretreatment with intraventricular injection of 1 μg of substance P in urethane anesthetized male rats. Thirty minutes after GABA injection the animals were decapitated and blood samples were collected from the trunk. Serum GH and prolactin were determined by radioimmunoassays. The intraventricular GABA elicited a significant increase in both serum GH and prolactin levels. Intraventricular substance P itself had no effect on serum GH and prolactin, but it inhibited the GABA-induced increases in serum GH and prolactin. Gamma-hydroxybutyric acid (GHB) was intraperitoneally injected with and without an intraventricular injection of substance P in urethane anesthetized rats. The GHB injection significantly increased serum GH and prolactin levels. Pretreatment with substance P completely inhibited the GHB-induced GH and prolactin responses. These results suggest that substance P might interact with GABA in the central nervous system.

Cimetidine inhibits the histamine-induced prolactin release in male rats.

SummaryThe specificity and mechanisms through which HA alters basal PR1 release were evaluated. Rats bearing atrial catheters were given icv infusions of histamine dihydrochloride or saline. Blood samples for PRL and LH were drawn before and at 15, 30, 45, and 60 min after infusion. Similar groups of animals were pretreated with icv infusions of diphenhydramine, cimetidine, atropine, or methysergide prior to icv HA. Animals given icv HA (90 μg) demonstrated at least a twofold rise in PRL at 15 min which fell to baseline levels at 45 min. Pretreatment with cimetidine, but not other agents, significantly inhibited the HA-induced rise in PRL. Serum LH was basically unaltered by these treatments. Histamine appears to be a specific stimulus to PRL release. This stimulatory effect of HA is inhibited by cimetidine, an H2 receptor blocker, but not by H1 receptor, cholinergic or serotoninergic antagonists.

Serotonergic control of prolactin release in male rats

To further clarify the relationship between the central serotonergic system and the control of prolactin secretion, we studied the effect of dorsal raphe' lesions, electrical stimulation of the midbrain raphe' nucleus and treatment with parachlorophenylalanine (PCPA) on prolactin secretion. Radio frequency destruction of serotonergic cell bodies in the midbrain dorsal raphe' nucleus or PCPA decreased forebrain serotonin (5HT) and 5-hydroxyindoleacetic acid (5HIAA) concentration and prolactin secretion. Electrical stimulation of the raphe' increased forebrain serotonin turnover and prolactin secretion. These observations indicate that serotonergic neurons located in the raphe' nuclei may be involved in regulating prolactin secretion in male rats.

Preoptic-hypothalamic control of LH and prolactin release in male rats under pentobarbital anesthesia: Differential responses to electrical stimulation

In acute experiments under pentobarbital anesthesia, the brains of adult male rats were stimulated bilaterally with trains of monophasic pulses at different frequencies and current intensities through bipolar, concentric, stainless steel electrodes. Stimulation of the POA-SQ region at 3, 10 (200 muA) or 200 Hz (100 muA) increased plasma prolactin levels within 30 min of the onset of stimulation. Stimulus parameters fully effective when applied to the POA-SQ or ARC-MED. EM. regions were ineffective when applied to the ARC-VMH region. Maximal effects were obtained with 10 Hz (200 muA) stimuli applied to the POA-SQ region. LH levels were increased after stimulation of any of the three regions--POA-SQ, ARC-VMH or ARC-MED. EM. Conversely to the prolactin response, LH levels did not rise after 3 Hz stimulation of the POA-SQ region. In male rats under pentobarbital anesthesia, LH levels seemed to be affected maximally with a stimulus frequency rate of about 50 Hz applied to the POA-SQ region. The results suggest a potential physiological role of frequency discrimination in the functional segregation of LH and prolactin release controls.