Opioid modulation of thyrotropin releasing hormone induced prolactin secretion

It is known that opioids stimulate prolactin (PRL) secretion by an action on hypothalamic neurons, but in vitro studies have suggested a direct action on the lactotrophs. The present study was performed on male rats known to have little or no PRL response to TRH. A beta-endorphin (beta EP) injection in the third ventricle stimulated PRL secretion and induced furthermore a PRL secretory reaction to TRH injected intravenously 20 min later. Pretreatment with naloxone 10 min before beta EP injection abolished not only the PRL response to beta EP but also the conjugated effect of beta EP and TRH. Pretreatment with naloxone methyl bromide (Br-naloxone), a quaternary naloxone derivative, which does not cross the blood-brain barrier, had no effect on the PRL response to beta EP but prevented the conjugated effect of beta EP and TRH on PRL secretion. Pretreatment of the animals with -methyl-parathyrosine resulting in a dopamine depletion or with haloperidol, a dopamine antagonist, could not induce lactotroph responsiveness to TRH. These results suggest that beta EP in male rat sensitizes the PRL cell to TRH by a direct effect and not through an inhibition of the dopaminergic tone.     

VIP enhances TRH-stimulated prolactin secretion of pituitary tumours. Studies with 31P NMR

Intravenous thyrotrophin releasing hormone (TRH) caused a 6.5-fold increase in plasma prolactin (PRL) in rats carrying implanted pituitary tumours. Vasoactive intestinal polypeptide (VIP) had no effect, but TRH given after VIP raised TRH stimulated secretion 13-fold above basal. 31P NMR spectroscopy showed that VIP caused a decrease in high energy metabolites (depleted phosphocreatine, elevated inorganic phosphate and lowered intracellular pH). TRH alone caused a similar but smaller effect; given after VIP, it caused no detectable depletion. We suggest that the changes in high energy metabolite concentrations reflect increased cellular energy consumption consistent with a priming process (stage 1) in PRL secretion, followed by hormone release (stage 2). VIP induces stage 1 whereas RTH induced both stages.     

Immunocytochemical localization of oviduct-specific glycoproteins in the oviductal epithelium from cows at follicular and luteal phases

An immunoelectron-microscopic and morphometric study was carried out on the anterior pituitary prolactin (PRL) cells of adult male Wistar rats treated with a combination of thyroidectomy and administration of L-thyroxine (T₄) and/or synthetic thyrotropin-releasing hormone (TRH) in order to clarify the effects of changes in the hypothalamus-pituitary-thyroid axis on the ultrastructure and function of PRL cells. After thyroidectomy, PRL cells underwent atrophy and hypofunction of their cell organelles, but these changes tended to be restored to their normal level by T₄ treatment. On the other hand, the administration of TRH to intact rats produced hypertrophy and hyperfunction in the PRL cells, although this treatment had no effect on the PRL cells of thyroidectomized rats. However, treatment with a combination of T₄ and TRH had a strong effect and led to hypertrophy and hyperfunction in the PRL cells of thyroidectomized rats. Serum and pituitary PRL levels were measured by radioimmunoassay (RIA) for a comparison with the morphological results. They correlated well with the morphological changes. These results indicate that TRH stimulates PRL secretion in the presence of thyroid hormone, and that the thyroid hormone plays an important role in the basic maintenance of PRL cell function and its reactivity to TRH.     

Catecholamines and pituitary function. III. Restoration of the prolactin response to thyrotropin-releasing hormone by low-dose dopamine infusion in women with pathological hyperprolactinemia

Previous studies in Rhesus monkeys have demonstrated that a dopamine (DA) infusion rate of 0.1 microgram/kg X min induces peripheral DA levels similar to those measured in hypophysial stalk blood and normalizes serum prolactin (PRL) levels in stalk-transected animals. We therefore examined the effect of such DA infusion rate on basal and thyrotropin-releasing hormone (TRH)-stimulated PRL secretion in both normal cycling women and women with pathological hyperprolactinemia. 0.1 microgram/kg X min DA infusion fully normalized PRL serum levels in 8 normal cycling women whose endogenous catecholamine synthesis had been inhibited by alpha-methyl-p-tyrosine (AMPT) pretreatment. Furthermore, DA significantly reduced, but did not abolish, the rise in serum PRL concentrations induced by both acute 500 mg AMPT administration and 200 micrograms intravenous TRH injection in normal women. A significant reduction in serum PRL levels in response to 0.1 microgram/kg X min DA, similar to that observed in normal cycling women when expressed as a percentage of baseline PRL, was documented in 13 amenorrheic patients with TRH-unresponsive pathological hyperprolactinemia. However, a marked rise was observed in the serum PRL of the same patients when TRH was administered during the course of a 0.1-microgram/kg X min DA infusion. The PRL response to TRH was significantly higher during DA than in basal conditions in hyperprolactinemic patients, irrespective of whether this was expressed as an absolute increase (delta PRL 94.4 +/- 14.2 vs. 17.8 +/- 14.1 ng/ml, p less than 0.002) or a percent increase (delta% PRL 155.4 +/- 18.9 vs. 17.9 +/- 7.1, p less than 0.0005), and there was a significant linear correlation between the PRL decrements induced by DA and the subsequent PRL responses to TRH. These data would seem to show that the 0.1-microgram/kg X min DA infusion rate reduces basal PRL secretion and blunts, but does not abolish, the PRL response to both TRH and acute AMPT administration. The strong reduction in PRL secretion and the restoration of the PRL response to TRH by 0.1 microgram/kg X min DA infusion in high majority of hyperprolactinemic patients, seem to indicate that both PRL hypersecretion and abnormal PRL response to TRH in women with pathological hyperprolactinemia are due to a relative DA deficiency at the DA receptor site of the pituitary lactotrophs.     

The effect of bombesin on basal, alpha-methyl-p-tyrosine, haloperidol, morphine, bremazocine and stress-induced prolactin secretion

Intravenously administered bombesin lowered basal PRL levels in conscious male rats and prevented the morphine, bremazocine and stress-induced PRL secretion. The same dose of bombesin had no effect on PRL levels in alpha-methyl-p-tyrosine pretreated rats and did not affect haloperidol-stimulated PRL release. These results show that bombesin given intravenously acts as an inhibitor of PRL secretion and suggests that it does not act on the lactotrope itself but rather by an increase of the inhibitory dopaminergic tone.     

17β-Estradiol modulates the prolactin secretion induced by TRH through membrane estrogen receptors via PI3K/Akt in female rat anterior pituitary cell culture

Considering that estradiol is a major modulator of prolactin (PRL) secretion, the aim of the present study was to analyze the role of membrane estradiol receptor-α (mERα) in the regulatory effect of this hormone on the PRL secretion induced by thyrotropin-releasing hormone (TRH) by focusing on the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway activation. Anterior pituitary cell cultures from female rats were treated with 17β-estradiol (E(2), 10 nM) and its membrane-impermeable conjugated estradiol (E(2)-BSA, 10 nM) alone or coincubated with TRH (10 nM) for 30 min, with PRL levels being determined by RIA. Although E(2), E(2)-BSA, TRH, and E(2)/TRH differentially increased the PRL secretion, the highest levels were achieved with E(2)-BSA/TRH. ICI-182,780 did not modify the TRH-induced PRL release but significantly inhibited the PRL secretion promoted by E(2) or E(2)-BSA alone or in coincubation with TRH. The PI3K inhibitors LY-294002 and wortmannin partially inhibited the PRL release induced by E(2)-BSA, TRH, and E(2)/TRH and totally inhibited the PRL levels stimulated by E(2)-BSA/TRH, suggesting that the mER mediated the cooperative effect of E(2) on TRH-induced PRL release through the PI3K pathway. Also, the involvement of this kinase was supported by the translocation of its regulatory subunit p85α from the cytoplasm to the plasma membrane in the lactotroph cells treated with E(2)-BSA and TRH alone or in coincubation. A significant increase of phosphorylated Akt was induced by E(2)-BSA/TRH. Finally, the changes of ERα expression in the plasmalemma of pituitary cells were examined by confocal microscopy and flow cytometry, which revealed that the mobilization of intracellular ERα to the plasma membrane of lactotroph cells was only induced by E(2). These finding showed that E(2) may act as a modulator of the secretory response of lactotrophs induced by TRH through mER, with the contribution by PI3K/Akt pathway activation providing a new insight into the mechanisms underlying the nongenomic action of E(2) in the pituitary.     

Effects of naloxone on basal and stress-induced prolactin secretion,in intact,hypothalamic deafferentated,adrenalectomized, and dexamethasone-pretreated male rats

The effects of naloxone (Nal) on basal and stress-induced PRL secretion were investigated in intact (N) adult male rats, as were its effects in rats with complete hypothalamic deafferentiation (CHD), in adrenalectomized (adrenX) rats, and in rats pretreated with dexamethasone (dex). Forty-five minutes subsequent to Nal administration (5mg/kg, BW, IP) basal serum levels of PRL were reduced by approximately 25% (p<0.05), in both N and CHD groups. PRL secretory responses to acute exposure to both photic and acoustic stress were markedly attenuated in Nal-injected, as compared to vehicle-injected animals. Basal serum PRL concentrations were elevated by 40% in adrenX rats (p<0.05), as compared to controls. In (p<0.05) in dex-treated rats, as compared to controls. In both these experimental groups, Nal administration caused significant reductions in serum PRL. This study demonstrates that stress-induced, as well as basal PRL secretion, is attenuated by Nal, and points to a hypothalamic site of action in this regard. Furthermore, these Nal effects are independent of glucocorticoid interactions with the CNS.     

Gluten exorphin B5 stimulates prolactin secretion through opioid receptors located outside the blood-brain barrier

Gluten exorphin B5 (GE-B5) is a food-derived opioid peptide identified in digests of wheat gluten. We have recently shown that GE-B5 stimulates prolactin (PRL) secretion in rats; this effect is abolished by preadministration of the opioid receptor antagonist naloxone. However, since the structure of naloxone allows it to cross the blood-brain barrier (BBB) and antagonize opioid effects centrally as well as peripherally, it could not established, on the basis of those data, if GE-B5-induced PRL release is exerted through sites located inside or outside the BBB. In this study, we sought to determine the site of action of GE-B5 on PRL secretion, by pretreating male rats with naloxone methobromide (NMB), an opioid antagonist that does not cross the BBB. Four groups of rats were given the following treatments: 1) intravenous vehicle; 2) intravenous GE-B5 (3 mg kg(-1) body weight); 3) intraperitoneal NMB (5 mg kg(-1) body weight), followed by vehicle; 4) NMB, followed by GE-B5. Blood samples for PRL were taken at intervals for 40 minutes after vehicle or GE-B5 administration. GE-B5 stimulated PRL secretion; the effect was statistically significant at time 20. NMB preadministration completely abolished PRL response. Our experiment indicates that GE-B5 stimulates PRL secretion through opioid receptors located outside the BBB. Since opioid peptides do not exert their effect on PRL secretion directly, but via a reduced dopaminergic tone, our data suggest that GE-B5 can modify brain neurotransmitter release without crossing the BBB.     

Effects of morphine on cold-induced TRH release from the median eminence of unanesthetized rats

The effect of morphine perfusion into the median eminence on cold-induced TRH secretion was studied in unanesthetized rats by push-pull cannulation. Perfusion with 10(-6)M morphine blocked the cold-induced TRH peak occurring about 40 min after the transfer of rats from 24 degrees C to 4 degrees C. This inhibition by morphine was blunted by concomitant administration of naloxone (10(-6)M or 10(-5)M), but naloxone alone had no effect on either basal or cold-induced TRH release. We conclude that specific opiate receptors may be located on TRH nerve endings in the ME, and that endogenous opiates may not have any physiological role in the cold-induced TRH response, at least during the two hours that follow cold exposure.     

Prolactin secretion after hypothalamic deafferentation in beef calves: response to haloperidol, alpha-methyl-rho-tyrosine, thyrotropin-releasing hormone and ovariectomy

In ruminant species photoperiod regulates prolactin (PRL) secretion. It is hypothesized that the inhibition of PRL secretion resides in dopaminergic neurons of the medial basal hypothalamus (MBH). To test this hypothesis, anterior (AHD), posterior (PHD) and complete (CHD) hypothalamic deafferentation and sham operation control (SOC) surgeries were carried out during May (long-day photoperiod) in beef heifer calves (6-8 mo old) to measure basal PRL secretion and PRL secretion as affected by intravenous secretagogues. On the day of surgery (day 0), PRL secretion reflected stress of anesthesia and surgery in all groups. Thyrotropin-releasing hormone (TRH), alpha-methyl-rho-tyrosine (alphaMrhoT), and haloperidol (HAL) was iv injected on days 11, 13 and 15, respectively. AHD, PHD, CHD, and SOC calves responded to TRH (100 microg) with an acute increase in PRL that peaked within 20 min. All heifers responded to alphaMrhoT (10 mg/kg BW) with an acute elevation in PRL within 10 min and remaining elevated for 3 h. HAL (0.1 mg/kg BW) induced an acute increase in PRL secretion in all groups, peaking within 15-30 min. Seven months later (December, short-day photoperiod) these heifers were ovariectomized. Basal plasma PRL levels were seasonally low, PRL secretion in AHD, PHD and CHD animals abruptly increased within 15 min to iv injection of 100 microg TRH to a greater amount than seen in SOC heifers. Although a biphasic effect on PRL secretion entrains under long-day and short-day photoperiods, hypothalamic deafferentation in cattle did not affect the pituitary gland's responsiveness to secretagogues.     

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.     

Differential involvement of protein kinase C in basal versus acetylcholine-regulated prolactin secretion in rat anterior pituitary cells during aging

Although it is well known that plasma concentration of prolactin (PRL) increases during aging in rats, how the anterior pituitary (AP) aging per se affects PRL secretion remains obscure. The objectives of this study were to determine if changes in the pituitary PRL responsiveness to acetylcholine (ACh; a paracrine factor in the AP), as compared with that to other PRL stimulators or inhibitors, contribute to the known age-related increase in PRL secretion, and if protein kinase C (PKC) is involved. We also determined if replenishment with aging-declined hormones such as estrogen/thyroid hormone influences the aging-caused effects on pituitary PRL responses. AP cells were prepared from old (23-24-month-old) as well as young (2-3-month-old) ovariectomized rats. Cells were pretreated for 5 days with diluent or 17beta-estradiol (E(2); 0.6 nM) in combination with or without triiodothyronine (T(3); 10 nM). Then, cells were incubated for 20 min with thyrotropin-releasing hormone (TRH; 100 nM), angiotensin II (AII; 0.2-20 nM), vasoactive intestinal peptide (VIP; 10(-9)-10(-5) M), dopamine (DA; 10(-9)-10(-5) M), or ACh (10(-7)-10(-3) M). Cells were also challenged with ACh, TRH, or phorbol 12-myristate 13-acetate (PMA; 10(-6) M) following PKC depletion by prolonged PMA (10(-6) M for 24 h) pretreatment. We found that estrogen priming of AP cells could reverse the aging-caused effects on pituitary PRL responses to AII and DA. In hormone-replenished cells aging enhanced the stimulation of PRL secretion by TRH and PMA, but not by AII and VIP. Aging also reduced the responsiveness of cells to ACh and DA in suppressing basal PRL secretion, and attenuated ACh inhibition of TRH-induced PRL secretion. Furthermore, ACh suppressed TRH-induced PRL secretion mainly via the PMA-sensitive PKC in the old AP cells, but via additional mechanisms in young AP cells. On the contrary, basal PRL secretion was PKC (PMA-sensitive)-independent in the old AP cells, but dependent in the young AP cells. Taken together, these results suggest differential roles of PMA-sensitive PKC in regulating basal and ACh-regulated PRL responses in old versus young AP cells. The persistent aging-induced differences in AP cell responsiveness to ACh, DA, TRH, and PMA following hormone (E(2)/T(3)) replenishment suggest an intrinsic pituitary change that may contribute, in part, to the elevated in vivo PRL secretion observed in aged rats.     

Serum prolactin in patients with Laron-type dwarfism: effect of insulin-like growth factor I.

Prolactin (PRL) secretion was studied in Laron-type dwarfism (LTD) patients (8 children and 9 adults) in basal condition, after acute insulin-like growth factor (IGF-I) or TRH injections and during 2 months of daily IGF-I treatment. Basal PRL was repeatedly higher (12.6 +/- 1.6 micrograms/l) than that in control subjects (7.6 +/- 1.2 micrograms/l, p < 0.05). Acute IGF-I injection caused an immediate slight decrease in serum PRL and growth hormone (GH), followed by a progressive rise to mean peak levels of 33.3 +/- 4.5 micrograms/l again parallel to serum hGH which rose to 86 +/- 20 micrograms/l--a response to the IGF-I-induced hypoglycemia. Intravenous TRH in LTD children induced a marked response in serum PRL, similar to that registered in estrogenized adult females. Serum PRL did not show consistent changes during chronic IGF-I treatment. It is suggested that the higher-than-normal PRL levels and release in LTD patients are due to a drift phenomenon of the mammosomatotropes which produce large amounts of hGH.     

Dual effect of osmotic cell swelling on prolactin secretion by acutely dispersed adenohypophyseal cells

Cell swelling induced by acute exposure to the permeant molecule urea or by medium hyposmolarity evoked a prompt PRL secretory burst from dispersed rat anterior pituitary cells. However, during continuous exposure greater than or equal to 10 min to these conditions inhibition of basal and TRH-induced PRL secretion occurred and there was an "off" burst of PRL secretion following return to basal conditions. Compared with continuous TRH stimulation which causes biphasic PRL secretion with a rapid high amplitude first phase secretory burst followed by a sustained low level second phase of secretion, cell swelling induced only "first phase" secretion. Removing Ca2+ from the medium or adding 50 microM verapamil markedly depressed the "off" secretory burst following return to basal conditions but had no effect on the initial high amplitude burst. Our data suggest that the effect of cell swelling on PRL secretion is complex and that there are at least two mechanisms for PRL secretion in normal anterior pituitary cells; these are differently affected by cell swelling and Ca2+ influx.     

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.     

Studies of anterior pituitary-grafted rats: I. Abnormal prolactin response to thyrotropin releasing hormone,clonidine, insulin,and fasting

Although the rat implanted with extra anterior pituitary glands (AP) under the kidney capsule has been widely used as a model of chronic hyperprolactinemia, its hormonal status has not been fully characterized. Using conscious, unrestrained female pituitary-grafted rats and sham-operated littermates, we investigated prolactin (PRL) secretion in response to the following stimuli: thyrotropin releasing hormone (TRH), clonidine, insulin, and fasting. The AP-implanted rats had a greater and more sustained rise in serum PRL after TRH than control rats, reflecting a direct effect of TRH on the ectopic lactotropes. In contrast after clonidine, which acts via the hypothalamus, the serum PRL rose to much higher levels in sham-operated rats than in rats bearing ectopic pituitary tissue. Both insulin-induced hypoglycemia and fasting decreased serum PRL in control rats, but the AP-implanted animals manifested a rise in serum PRL in response to these stimuli. Thus, the AP-implanted rat is not only a valid model of excess and abnormal PRL secretion, but it may also be useful for distinguishing between stimuli requiring an intact hypothalamic-pituitary unit and agents which act directly on the pituitary gland.     

Dopamine control of aldosterone secretion in end-stage renal failure

The role of the tonic inhibitory effect of dopamine on aldosterone secretion has been investigated in 10 patients with chronic renal failure (CRF) on hemodialysis, in 8 normotensive renal transplant recipients (Tx) with normal renal function and in 8 normotensive volunteers (NV). The following tests were performed: the response of plasma aldosterone (PA) to metoclopramide administration; the response of plasma prolactin (PRL) to TRH administration, and the changes induced by Lisuride (a dopaminergic agonist, on the values of PA and PRL). The basal values of PA and PRL were higher in CRF than in NV and Tx. The inverse was true for plasma renin activity (PRA) values. The response of PA and PRL to metoclopramide showed blunted increases in CRF when compared to NV, in the absence of changes of PRA, cortisol and potassium. After TRH administration, PRL increase in CRF was also inferior. Lisuride induced a decrease of both PA and PRL both in CRF and NV. In Tx, basal values of PA and PRL were similar to NV. Nevertheless, the response to metoclopramide and TRH were partially blunted when compared to that of NV. These results point to the existence of a deranged dopaminergic regulation of aldosterone secretion in end-stage renal failure patients. The alterations are partially corrected by a well-functioning kidney graft.     

Effects of in vivo pretreatment with D-Trp-6-LH-RH on prolactin and LH secretion by pituitary glands in vitro

In order to study a possible direct action of LH-RH analogs on the pituitary lactotrophs, we investigated the effect of long-term in vivo pretreatment with D-Trp-6-LH-RH on in vitro secretion of PRL and luteinizing hormone (LH) by the pituitary glands from male and female rats. In vivo pretreatment with D-Trp-6-LH-RH (50 micrograms/day, SC) for 15 days greatly reduced basal in vitro PRL release (p less than 0.01) in female, but not in male pituitary glands. TRH-stimulated PRL secretion was not affected by pretreatment with D-Trp-6-LH-RH in female rats, but was impaired in male pituitaries. Acute in vitro exposure to D-Trp-6-LH-RH did not modify PRL secretion by female pituitary glands pretreated in vivo with the analog. However, this same in vivo pretreatment greatly decreased PRL release from male pituitaries (p less than 0.01). Basal in vitro LH release by male pituitary glands was partially lowered by in vivo pretreatment with D-Trp-6-LH-RH, as compared to controls (p less than 0.01), while basal LH release in female pituitaries remained at control levels. Finally, D-Trp-6-LH-RH-induced stimulation of in vitro LH release was severely impaired in female pituitaries (p less than 0.01) but only slightly reduced in the males.     

Somatostatin inhibits prolactin secretion in the estradiol primed male rat

Somatostatin inhibits not only growth hormone secretion, but also the secretion of several other hormones. The role of somatostatin in prolactin (PRL) secretion has not been clearly demonstrated. The present study was undertaken to examine the effects of somatostatin on rat PRL secretion in several different circumstances where the circulating PRL level is elevated: (1) the estradiol primed intact male rat, (2) normal and (3) estradiol primed rats pretreated with pimozide, (4) normal and (5) estradiol primed hypophysectomized male rats with adenohypophyses grafted under the kidney capsule (HAG rat). Blood samples (70 microL) were taken every 2 min via an indwelling atrial cannula from conscious, unrestrained animals. In the estradiol primed intact rats, a bolus injection of somatostatin (10, 100, and 1000 micrograms/kg) lowered PRL levels in a dose-dependent manner. When the PRL concentration was elevated by the administration of pimozide (3 mg/kg), a dopaminergic receptor blocking agent, somatostatin was ineffective in decreasing plasma PRL concentration but the PRL concentration was lowered by somatostatin when the rat had been primed with estradiol. Somatostatin had no effect on the normal HAG rats, but lowered the plasma PRL concentration in the estradiol primed HAG rats. Since somatostatin inhibits PRL secretion only in the estradiol primed rats, it is suggested that estradiol priming creates a new environment, presumably via new or altered receptors, which can be inhibited by somatostatin.     

Impairment of stress-induced secretion of prolactin during development: effects of adrenalectomy, TRH and sulpiride

Ontogeny of serum and anterior pituitary gland PRL contents was investigated. Pituitary PRL concentrations were found to be low in fetus by 19th day of gestation and to rise slowly after birth with no sex differences being apparent until day 30. Adult levels were reached in males on day 15, while in females they were reached beyond this stage. Serum PRL levels exhibited a similar developmental pattern. In adult rats ether stress stimulated basal serum PRL significantly, with maximum effect one minute after onset of stress. The same pattern was seen with immature animals of 15-20 and 30 days of age. In contrast, in 2 or 6 day-old neonates, serum PRL concentrations remained unaffected by stress. This lack of responsiveness suggests the existence of a transient impairment of lactotrophs to respond to stressful stimuli during postnatal life. Adrenalectomy increased PRL release in adult and newborn rats from day 15 onward and potentiated the response of lactotrophs. Moreover, after adrenalectomy, 6 day-old rats became sensitive to ether stress, while acute treatment with dexamethasone abolished completely this response. In adult or 15 day-old neonates administration of TRH or sulpiride resulted in a marked increase in serum PRL levels. However, at 6 days TRH did not affect resting serum PRL concentrations significantly, whereas sulpiride remained efficient. Moreover, at this age, dopamine inhibited stress-induced PRL release and reduced the stimulatory effect of sulpiride.(ABSTRACT TRUNCATED AT 250 WORDS)