Idazoxan inhibits hyperprolactinaemia in ovariectomized estrogen-treated rats

The alpha 2-antagonist idazoxan (IDZ) has previously been shown to inhibit hyperprolactinaemia triggered by various stimuli such as lactation, stress, serotonergic agents and morphine (Preziosi, Martire, Navarra, Pistritto and Vacca 1989; Krulich, Jurcovicova and Le 1989). In this study, we investigated the PRL-lowering activity of IDZ in ovariectomized estrogen-treated (OET) rats; since a PRL surge usually occurs in normal cycling rats on the day of proestrus, the effect of IDZ on pulsatile PRL release in intact female rats was also studied. IDZ significantly lowered plasma PRL levels in OET rats; no elevated PRL values were observed in normal cycling rats, indicating that IDZ might inhibit PRL surges in these animals. It is concluded that IDZ is an effective PRL-lowering agent in a number of physiological and pharmacological hyperprolactinaemic models.     

Prolactin (PRL) release-inhibiting properties of the alpha 2 adrenergic receptor antagonist idazoxan: comparison with yohimbine

The effects of the alpha 2 adrenergic receptor antagonists yohimbine (YOH) and Idazoxan (ID) on secretion of PRL were compared in nonanesthetized male rats bearing permanent intraatrial cannulae for i.v. drug delivery and serial blood sampling. YOH induced a dose-related elevation of basal plasma PRL levels. ID had either no effect or a tendency to lower them and effectively inhibited stimulation of PRL secretion with morphine, 5-hydroxytryptophan (5HTP), quipazine or restraint stress. YOH at low doses did not alter the PRL secretory responses to these stimuli or enhanced them at the highest dose used (1.56 mg/kg). ID inhibited the PRL-stimulating, effect of 5HTP or morphine following inhibition of NE synthesis with FLA63 or pretreatment with clonidine. It also blocked the effect of quipazine in rats pretreated with prazosin. It is concluded that ID, in a complete contrast to YOH effectively inhibits PRL secretion. The inhibitory mechanism appears to be unrelated to its interaction with the alpha adrenergic receptors.     

Possible involvement of endogenous opioid peptides in prolactin secretion induced by alpha 2-adrenergic stimulation in rats

Noradrenergic mechanisms have a stimulatory role in regulating prolactin (PRL) secretion in the rat. We investigated the mechanism by which the alpha 2-adrenergic system stimulates PRL release in urethane-anesthetized male rats. Intracerebroventricular injection of norepinephrine (2 micrograms/rat) or epinephrine (100 ng and 1 microgram/rat) caused an increase in plasma PRL levels. The PRL increase induced by epinephrine was much greater than that by norepinephrine. Intracerebroventricular injection of phentolamine (1 microgram/rat), an alpha-antagonist, blunted the plasma PRL increase induced by epinephrine (100 ng intracerebroventricularly). Plasma PRL levels were increased by intravenous injection of alpha 2-agonists, clonidine (15 micrograms/100 g of body wt), and xylazine (200 micrograms/100 g of body wt). Plasma PRL increase induced by clonidine or xylazine was suppressed by intravenous injection of naloxone (125 micrograms/100 g of body wt), an opiate antagonist. These findings suggest that alpha 2-adrenergic mechanisms stimulate pituitary PRL secretion, at least partly, by activating endogenous opioid peptides in the rat.     

Lipolysis in rat adipose tissue in vitro and its alpha 2 adrenergic control

Although the alpha 2-adrenergic inhibitory control on lipolysis in several mammalian species, e.g. in dogs, hamsters, rabbits and also in man has been proved recently, in rats some peculiarities have been described in the alpha-adrenergic regulation of lipid mobilization. In the present study the effect of the specific alpha 2-adrenergic blocking agent--yohimbine (YOH)--on lipid mobilization in young (45-55 days old) and old (6 months) rats of the Wistar strain was followed and also its interaction with the beta-adrenergic blocking agent propranolol and the specific alpha 2-adrenergic agonist--clonidine. Furthermore, the effect of YOH on the isoprenaline (ISO) induced lipolysis was studied. The adipokinetic effect was estimated from the amount of released non-esterified fatty acids from the tissue preparation into the incubation medium. In all experimental series YOH produced a significant response, which was concentration-dependent (pD2 6.2) with the maximum effect corresponding to 40% of the highest adipokinetic action of ISO. Young rats were more sensitive than old animals. In both age groups YOH non-competitively decreased the highest effect of ISO to the level of its own lipid-mobilizing activity. In the presence of YOH, the ISO dose-response curve therefore completely disappears. The adipokinetic effect of YOH can be antagonized competitively by clonidine (CLO) (pA2 6.25 and 6.01 for concentrations of CLO 1 and 10 mumol.1(-1) respectively). The inhibitory effect of propranolol is about two orders lower. It is concluded that in rats the alpha 2-adrenergic control rather concerns basal lipolysis, whereas induced lipid mobilization can be inhibited by depression of the alpha 2-activity.     

Further evidence for the inhibitory action of baclofen on a prolactin-releasing factor

The mechanism of action of a specific gamma-aminobutyric acid B receptor agonist, beta-p-chlorophenyl-gamma-aminobutyric acid or baclofen, in its inhibitory action on prolactin release, was studied. Dose-response studies of the effect of baclofen on prolactin (PRL) secretion were performed in stressed male rats. Furthermore, the action of the drug was evaluated in (i) rats treated with haloperidol or alpha-methyl-p-tyrosine, (ii) stressed or suckled rats pretreated with sulpiride, and (iii) animals treated with serotonin, alone, or with alpha-methyl-p-tyrosine. Baclofen showed a clear dose-dependent inhibition of prolactin secretion in males under stress. The drug was unable to inhibit the prolactin release induced by haloperidol or alpha-methyl-p-tyrosine, although it reduced the PRL secretion induced by serotonin. It also inhibited PRL release in sulpiride-pretreated stressed or suckled rats. These results suggest that the dose-dependent effect of baclofen on PRL secretion is the consequence of an inhibition exerted on the prolactin-releasing factor component of the neuroendocrine responses evoked by stress or suckling, possibly acting at the serotonergic system.     

A comparison of the effects of suckling or transient dopamine antagonism on thyrotropin-releasing hormone and suckling induced prolactin release in lactating rats

Prolactin (PRL) release was studied in mid-lactational female rats by comparing the stimulatory influence of suckling to a drug protocol that mimics the effect of suckling on the anterior pituitary (AP). Animals that nursed pups for 15 minutes and were allowed to suckle again 60 minutes later for 10 minutes, released PRL effectively during both nursing episodes; however, in animals that received the dopamine (DA) agonist 2-Br-alpha-ergocryptine maleate (CB-154, 0.5 mg/rat i.v.) at the end of the first nursing period did not show an increase in plasma PRL to a second suckling stimulation by the pups. When thyrotropin releasing hormone (TRH) was substituted for the second suckling period in CB-154 treated rats, a slight increase in plasma PRL occurred 5 minutes after the injection. In a third study we transiently blocked the action of DA at the AP by injecting the DA antagonist domperidone (0.01 mg/rat i.v.), followed 5 minutes later by the administration of CB-154. One hour later animals were either allowed to suckle pups for 10 minutes or were injected with TRH. Treatment with TRH resulted in an 11 fold increase in plasma PRL but suckling was completely ineffective in inducing PRL release. These data suggest that the lack of PRL release to suckling in CB-154 treated rats was due to inhibitory effects of CB-154 on neural mechanisms which link nursing to PRL release. In addition, the data show that pharmacologic DA antagonism affects TRH releasable PRL more than does suckling. This may be due to a reduction, by suckling, of the pool of PRL that is available to be released by TRH administration.     

Stimulation of prolactin secretion by morphine: role of the central serotonergic system.

Unanesthetized male rats with indwellinh right atrial cannulae were injected with morphine (MOR) i.v. which produced a dose-related increase in plasma prolactin levels (PRL). This effect was blocked partially by naloxone (NAL) at a dose of 0.06 mg/kg and totally by 0.6 mg/kg NAL. Interruption of central serotonergic neurotransmission by receptor blockade, with metergoline (MET) or cyproheptadine (Cypro), inhibition of tryptophan hydroxylase by para-chlorophenylalanine or destruction of serotonin neurons by 5, 7-dihydroxytryptamine antagonized the morphine (3 mg/kg) induced elevation in PRL release. Depression of dopaminergic activity with α-methyl-para-tyrosine elevated the basal PRL levels, but it did not prevent a further increase of prolactin levels by morphine (3 mg/kg). These data are compatible with the hypothesis that morphine stimulates PRL release by activation of the central serotonergic system.     

Effect of passive immunization against substance P in rats with hyperprolactinemia

Substance P, an undecapeptide isolated from gut and brain tissues, was reported to stimulate prolactin release. It was suggested that substance P may play a role in the control of prolactin secretion. In this investigation we studied the effects of the blockade of endogenous substance P by the administration of a specific anti-substance P serum on serum prolactin levels in rats in the evening of proestrus, in lactating rats after suckling, and in male rats with hyperprolactinemia induced by grafting 2 anterior pituitary glands under the kidney capsule. The injection of the anti-substance P serum was followed by a significant decrease of the prolactin surge induced by 30 min suckling in lactating rats, when the antiserum was administered 24 hr but not 5.30 hr earlier. Anti-substance P serum also induced a significant decrease in serum prolactin levels in pituitary grafted rats, but induced no change in the proestrous surge of prolactin and LH. These results show that substance P may be involved in the release of prolactin induced by suckling and that this peptide may have an intrapituitary role in the process of prolactin release. On the other hand, substance P does not seem to play a significant role in the proestrous peak of prolactin and LH.     

Effects of treatment of normal and hyperprolactinemic rats with cyclosporine in vivo on the release of gonadotropins and prolactin from their pituitaries in vitro.

Cyclosporine (CyA) is extremely useful as an immunosuppressant and it is believed that at least some of its actions are due to antagonizing PRL effects. To determine whether the reported ability of CyA to inhibit gonadotropin release can be modified by PRL, we have examined the effects of treatment of normal and hyperprolactinemic rats with CyA in vivo on the release of LH, FSH and PRL from their pituitaries in vitro. Hyperprolactinemia was induced by implantation of capsules containing diethylstilbestrol (DES) and the animals were examined while the capsules were still in place (DES-IN) or after they had been removed (DES-OUT). Treatment with CyA significantly reduced plasma LH levels in control DES-IN rats without reducing basal LH release from the pituitaries of these animals in vitro. In the DES-IN rats, CyA exposure in vivo did not modify plasma PRL levels, but reduced PRL release in vitro, and interfered with the inhibitory action of dopamine (DA) on PRL release. The effect of DA on gonadotropin release in vitro was modified by CyA treatment. Administration of CyA failed to antagonize the suppressive effects of hyperprolactinemia on plasma LH and FSH levels or on the basal rates of gonadotropin release by incubated pituitaries. We conclude that CyA can reduce PRL release but does not interfere with the actions of PRL on anterior pituitary function.     

Effects of hyperprolactinemia on rat prostate growth: evidence of androgeno-dependence

The effects of the polypeptide hormone prolactin (PRL) in the development and regulation of benign prostate hyperplasia (BPH) and also in prostate cancer are not very well characterized. This study examines the action of PRL, either alone or in association with androgens [testosterone (T) or dihydrotestosterone (DHT)], in the rat prostate gland. The effects of PRL and androgens were investigated after 30 and 60 days in control, castrated, castrated with a substitutive implant of T or DHT, and sham-operated Wistar rats. To enhance PRL release, we induced hyperprolactinemia by administering chronic injections of sulpiride (40 mg. kg(-1). day(-1)). Chronic hyperprolactinemia induces enlargement and inflammation of the lateral rat prostate without any histological changes on ventral and dorsal lobes. We also demonstrate that hyperprolactinemia induces Bcl-2 overexpression in the lateral rat prostate and that this could inhibit the level of apoptosis. The in vivo model established here is a useful in vivo approach for studying the hormonal regulation of normal and pathological prostate development.     

The effects of dopaminergic antagonism by sulpiride on TRH and VIP-induced prolactin release in nonsuckled lactating rats

Prolactin (PRL) release was studied in female rats during midlactation using pharmacologic manipulations designed to mimic the hypothalamic effects of suckling. In the first experiment pituitary dopamine (DA) receptors were blocked by sulpiride (10 micrograms/rat i.v.). One hour later, thyrotropin-releasing hormone (TRH, 1.0 micrograms/rat i.v.) was given to induce PRL release. TRH released significantly more PRL following DA antagonism than when no DA antagonism was produced, suggesting that DA receptor blockade increased the sensitivity of the AP to TRH. In a second experiment, VIP (25 micrograms/rat) increased plasma prolactin 3-4 fold but this effect was not enhanced significantly by prior dopamine antagonism with sulpiride. We conclude that dopamine antagonism enhances the PRL releasing effect of TRH but not VIP in lactating rats.     

α2-Adrenergic stimulation enhances growth hormone secretion in the dog: A presynaptic mechanism?

Intravenous administration of clonidine (CLO), (2,4 and 8/micrograms/Kg), a predominantly alpha 2-adrenergic receptor agonist, induced in unanesthetized dogs clear-cut and dose-related rises in plasma GH (cGH) levels. Pretreatment with the selective antagonist of alpha 1-adrenergic receptors prazosin (0.1 mg/Kg iv) left unaltered the cGH rise induced by 4/micrograms/Kg of CLO whilst blockade of alpha 2-adrenergic receptors by yohimbine (2.5 mg/Kg iv) completely prevented it. In dogs treated 24 h previously, with reserpine (0.5 mg/Kg iv), a depletor of brain catecholamine stores, CLO was ineffective to stimulate cGH release. These data indicate that in the dog the GH-releasing effect of CLO occurs via stimulation of alpha 2-adrenergic receptors and suggest that the latter are located presynaptically in relation to norepinephrine neurons.     

Prolactin stimulates the L-type calcium channel-mediated transepithelial calcium transport in the duodenum of male rats

Elevated plasma levels of prolactin (PRL) have been reported in several physiological and pathological conditions, such as lactation, prolactinoma, and dopaminergic antipsychotic drug uses. Although PRL is a calcium-regulating hormone that stimulates intestinal calcium absorption in lactating rats, whether PRL is capable of stimulating calcium absorption in male rats has been elusive. Herein, the transepithelial calcium transport and electrical characteristics were determined in ex vivo duodenal tissues of male rats by Ussing chamber technique. We found that PRL receptors were abundantly present in the basolateral membrane of the duodenal epithelial cells. PRL (200–800 ng/mL) markedly increased the active duodenal calcium transport in a dose-dependent fashion without effect on the transepithelial resistance. The PRL-enhanced active duodenal calcium transport was completely abolished by L-type calcium channel blocker (nifedipine) as well as inhibitors of the major basolateral calcium transporters, namely plasma membrane Ca²⁺-ATPase and Na⁺/Ca²⁺ exchanger. Several intracellular mediators, such as JAK2, MEK, PI3K and Src kinase, were involved in the PRL-enhanced transcellular calcium transport. Moreover, PRL also stimulated the paracellular calcium transport in the duodenum of male rats in a PI3K-dependent manner. In conclusion, PRL appeared to be a calcium-regulating hormone in male rats by enhancing the L-type calcium channel-mediated transcellular and the paracellular passive duodenal calcium transport. This phenomenon could help restrict or alleviate negative calcium balance and osteoporosis that often accompany hyperprolactinemia in male patients.     

Effects of specific alpha-adrenoceptive agents on extraneuronal uptake (uptake2) of isoproterenol in perfused rat heart

Effects of specific alpha-adrenoceptive agents (alpha 1-agonist, alpha 1-antagonist, alpha 2-agonist and alpha 2-antagonist) on the extraneuronal accumulation of 3H-isoproterenol in the perfused rat heart were examined. The extraneuronal accumulation of 3H-isoproterenol in the hearts perfused with 3H-isoproterenol (10(-6)M) under COMT inhibition by tropolone (10(-4)M) was about 6 times higher than that of intact COMT. The increase in the accumulation by COMT inhibition was regarded as 100% and the effects of specific alpha-adrenoceptive agents on the accumulation was evaluated. alpha 1-agonists, methoxamine and phenylephrine, did not affect the accumulation. alpha 1-antagonists, prazosin, bunazosin and YM-12617, significantly decreased the accumulation of 3H-isoproterenol and these IC50 values were 2 x 10(-6)M, 3.5 x 10(-6)M and 2.3 x 10(-5)M, respectively. alpha 2-agonists, clonidine and guanabenz, significantly reduced the accumulation and these IC50 values were 3.4 x 10(-5)M and 2.9 x 10(-7)M, respectively. The alpha 2-antagonist, yohimbine, did not affect the accumulation. The present experiments clearly demonstrated that the tested alpha 1-antagonists and alpha 2-agonists inhibited uptake2 in rat heart but the tested alpha 1-agonists and an alpha 2-antagonist did not inhibit it.     

Catecholamines and pituitary function. VII: Effects of acute and chronic dopamine-receptor blockade on pituitary response to TRH-GNRH in normal women and in patients with hyperprolactinemic amenorrhea

To investigate whether an enhanced dopamine (DA) inhibition on pituitary thyrotrophs and gonadotrophs may account for the abnormal TSH and LH dynamics in pathological hyperprolactinemia, we examined the effect of an acute lysis of the putative DA overinhibition, as obtained with continuous domperidone (DOM) infusion, on both basal and TRH-GnRH stimulated PRL, TSH and LH release in both normal cycling women and patients with pathological hyperprolactinemia. The effect of TRH-GnRH administration was also examined in women with DA-antagonist induced hyperprolactinemia, in order to evaluate the effect of a chronic lack of the physiological DA inhibition on pituitary hormone dynamics. Patients with both pathological and DA-antagonist induced hyperprolactinemia displayed an evident TSH and LH hyper-responsiveness to TRH-GnRH. The PRL response was reduced in the former but enhanced in the latter group. Domperidone infusion resulted in a marked increase in serum PRL levels in normal cycling women, but not in patients with pathological hyperprolactinemia. The abolition of the putative DA-overinhibition at the pituitary level with DOM infusion in patients with pathological hyperprolactinemia was followed by a slight increase in basal TSH output but did not modify the TSH and LH hyperresponsiveness to TRH-GnRH. The similarities in TSH and LH dynamics between patients with pathological and DA-antagonist induced hyperprolactinemia and the ineffectiveness of DOM infusion in modifying the TSH and LH hyper-responses to TRH-GnRH in the former group, seem to exclude the widely accepted idea that endogenous DA overactivity is responsible for the abnormal thyrotroph and lactotroph dynamics in women with hyperprolactinemic amenorrhea.     

Presynaptic alpha 2 -adrenergic stimulation leads to growth hormone release in the dog

In previous studies we have shown that the alpha 2 -adrenergic receptor agonist clonidine (CLON) releases growth hormone (GH) in conscious dogs, an effect abolished by the selective alpha 2-receptor antagonist yohimbine (YOH) and by reserpine, but not by the alpha 1-receptor antagonist prazosin (1). In the present work intravenous (iv) administration of CLON in conscious dogs evoked a dose-related rise in plasma GH at doses of 2-8 /micrograms/Kg, but not at 16 and 32 /micrograms/Kg. Acute pretreatment with the selective inhibitor of norepinephrine (NE) synthesis, DU-18288, or with a potent antagonist of presynaptic alpha 2-receptors, mianserin abolished the GH rise induced by CLON (4 /micrograms/Kg iv). In contrast, a 10-day-pretreatment with YOH greatly enhanced the GH-releasing effect of CLON (2 /micrograms/Kg iv). In all these data indicate that in the dog: 1) CLON induces GH release via activation of alpha 2-adrenergic receptors; 2) these receptors are likely located on presynaptic sites [experiments with reserpine (1), DU-18288, mianserin, dose-response curve with CLON 2-32/micrograms/kg iv]; 3) the adrenergic receptors involved in GH release exhibit supersensitivity upon (YOH-induced) chronic pharmacologic denervation. In view of the inhibitory action of presynaptic alpha 2-adrenergic receptors (autoreceptors) on NE function, it may be envisioned that in the dog noradrenergic activation is inhibitory and not stimulatory to GH release.     

Presynaptic alpha-adrenoceptor regulation of transmitter release in the conscious rat

1. Blood pressure (BP) and heart rate (HR) were recorded in conscious, adrenal demedulated rats. The rats were subjected to a 1-min period of mild "stress", induced by jet-air directed into the experimental cage. The plasma content of noradrenaline (NA), dopamine (DA) and 3, 4-dihydroxy-phenylacetic acid (DOPAC) was determined 1 min after termination of "stress". 2. The presynaptic alpha 2-adrenoceptor antagonist yohimbine (YOH) (10(-7) - 10(-6) mol/kg, given 5 min prior to "stress") did not alter the increase in BP and HR, induced by "stress", when compared to control rats (receiving NaCl instead of YOH at the corresponding time). 3. Pre-treatment with atropine (ATR) (2.5 mg/kg) 5 min before YOH (10(-6) mol/kg) or NaCl increased HR but not BP significantly in both groups of rats. "Stress", as above, gave a significant prolongation of the increase in HR in rats receiving YOH, when compared to control rats. The increase in BP was not significantly altered, compared to controls. 4. The neuronal re-uptake inhibitor desmethylimipramine (DMI) (0.1 mg/kg) was given together with ATR (2.5 mg/kg) 5 min before YOH (10(-6) mol/kg) or NaCl in one group of rats. This treatment induced a significant increase in HR but did not affect BP. "Stress", induced as above, extended the duration of the increase in HR in the YOH-treated rats, compared to controls. The increase in BP was not significantly different between the YOH-treated rats and the controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Central inhibitory action of TRH on prolactin secretion in the rat

Intravenous (iv) injection of FK33-824 [( D-Ala2, MePhe4, Met-(O)5-ol]-enkephalin, 8 and 16 nmole/100 g body wt), a potent Met5-enkephalin analog, and domperidone (1.2, 2.4, and 24 nmole/100 g body wt), a dopamine antagonist, resulted in a dose-related increase in plasma prolactin (PRL) levels in urethane-anesthetized male rats. PRL release induced by FK33-824 (16 nmole/100 g body wt, iv) was inhibited by intraventricular (icv) injection of TRH (0.6 nmole/rat). DN-1417 (gamma-butyrolactone-gamma-carbonyl-histidyl-prolinamide citrate, 0.6 nmole/rat, icv), a TRH analog, also blunted PRL release induced by FK33-824. PRL release induced by a smaller dose of domperidone (1.2 nmole/100 g body wt, iv) was blunted by TRH and DN-1417, whereas both peptides failed to suppress elevated PRL levels induced by larger doses of domperidone. These results suggest that TRH not only stimulates PRL secretion by acting directly at the pituitary, but has an inhibitory action on PRL release through activation of the central dopaminergic mechanism.     

Characterization of an in vitro method for demonstrating thyrotropin-releasing hormone-stimulated prolactin secretion.

Anterior pituitaries of normal adult male rats were subjected to synthetic thyrotropin-releasing hormone (TRH) treatment in an acute incubation system which employed pretreatment of the glands with plasma obtained from the donor animals. Following a 60-min preincubation period in a 1:1 mixture of Krebs-Ringer bicarbonate buffer (KRB) and plasma, media and hemipituitary prolactin (PRL) concentrations were significantly (p less than 0.01) increased after a 40-min treatment with 500 pg TRH. The TRH effect was absent among hemipituitaries preincubated in KRB alone. Plasma obtained from older donors was more potent than was plasma from younger rats in this effect. TSH secretion was markedly increased by 500 pg TRH, whether or not plasma preincubation was employed. A dose response of PRL release to concentrations of TRH from 100 pg to 6.0 ng was observed. Crude extracts of median eminence also effected enhanced PRL release using the plasma preincubation technique. The results suggest that plasma preincubation of explanted pituitaries increases PRL cell sensitivity to TRH, perhaps by enzymatic inactivation of endogenous TRH bound to cellular membrane receptors.     

Effect of Pituitary Graft-Induced Hyperprolactinemia on Adrenal Orcadian Rhythmicity

Prolactin is involved in the regulation of several endocrine functions. In this study, the possible influence of hyperprolactinemia on circadian corticosterone secretion has been investigated. Pituitary grafted male and female rats exhibited increased plasma PRL levels at 1000 when compared to sham-operated controls. This increase was only maintained over the 24 h period in grafted female rats but not in males, thus suggesting a different sex dependent modification of the regulatory mechanisms of prolactin. The corticosterone secretion pattern in sham operated male and female rats was similar to those described earlier but was altered by hyperprolactinemia according to the sex of the animal. There was a significant decrease in the total amount of corticosterone secreted in a 24 h period in grafted males as compared to control animals, whereas no significant differences were observed in grafted female rats as compared to controls. Grafted females showed a 4 h delay in the 24 h secretion rhythm as compared to control animals. These data suggest that pituitary transplant induced hyperprolactinemia, directly or through modifications in catecholamine turnover, is able to modify adrenal rhythmicity.