Acute stimulation of prolactin release by estradiol: mediation by the posterior pituitary

We have previously shown that the posterior pituitary contains a potent PRL-releasing factor (PRF). Estradiol stimulates PRL release by acting at three possible sites: the hypothalamus, the anterior pituitary, and the posterior pituitary. The objectives were 1) to document the profiles of PRL and LH release in response to an acute administration of estradiol, and 2) to identify the site of action of estradiol by employing two surgical approaches, pituitary stalk section (SS) and posterior pituitary lobectomy (LOBEX). Ovariectomized rats were used throughout. In Exp 1, rats were injected iv with 5 micrograms/kg 17 beta-estradiol, and blood was collected at 30-min intervals for 4 h. Estradiol induced a rapid and profound decline in plasma LH levels and a delayed, 5- to 6-fold rise in PRL. The purpose of the second experiment was to determine whether estradiol stimulates PRL release by acting at the anterior pituitary. Injection of estradiol to SS rats failed to stimulate a rise in PRL. We have previously reported that lactotrophs of SS rats are responsive to PRL secretagogues such as TRH. The objective of the third experiment was to differentiate between hypothalamic and posterior pituitary sites of estradiol action. Estradiol induced only a small rise in PRL when injected into LOBEX rats. However, LOBEX and control rats showed similar large rises in PRL in response to injection of alpha-methyl-para-tyrosine, an inhibitor of tyrosine hydroxylase. The latter indicates that the hypothalamic dopaminergic system as well as anterior pituitary lactotrophs are functionally intact in LOBEX rats. We conclude that estradiol administration to ovariectomized rats induces a rapid decline in LH and a delayed marked increase in PRL. The posterior pituitary, probably via PRF, is the primary site that mediates the acute effects of estradiol on PRL release. Estradiol does not stimulate PRL release directly from the anterior pituitary. The role of the hypothalamus is unclear. Estradiol could act directly on PRF-containing cells in the posterior pituitary or indirectly, via hypothalamic neurons terminating in the posterior pituitary. The hypothalamus also has a minor component that responds to estradiol and is independent of the posterior pituitary.     

Distribution of immunoreactive prolactin in the male and female rat brain: effects of hypophysectomy and intraventricular administration of colchicine

Immunohistochemical studies have identified immunoreactive prolactin (IR-PRL) in the hypothalamus and other areas of the rat brain. However, immunocytochemical techniques make it difficult to quantify the amount of antigen localized in a specific region. In this study, IR-PRL was extracted from selected regions of the rat brain, consisting of the median eminence, dorsal and ventral hypothalamus, thalamus, amygdalae, cerebellum, cortex, hippocampus, septum, pons-medulla, and olfactory lobes, and the concentrations of IR-PRL were determined by radioimmunoassay. Whereas IR-PRL was detected in all brain regions in both the male and the female rat brain, the concentrations of IR-PRL in the female rat were significantly greater than those measured in the corresponding region of the male rat brain. In the female rat, hypophysectomy significantly reduced, but did not eliminate, the concentration of IR-PRL in hypothalamus, amygdala, thalamus, and pons-medulla. In contrast, hypophysectomy did not affect the concentration of IR-PRL in any brain regions of the male rat. Injection of colchicine into the lateral ventricle decreased the concentration of IR-PRL in the median eminence and increased the concentration of IR-PRL in the ventral hypothalamus in male and female rats. In addition, extracted hypothalamic and pituitary IR-PRL displayed similar dilution curves in the PRL assay and elution patterns on Sephadex G-100. These data indicate that both the male and the female rat brain contains an IR-PRL-like material with physicochemical properties similar to those of pituitary PRL. This material is differentially distributed in the male and female brain and is found in greater concentrations in the female brain.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hormonal control of tyrosine hydroxylase in the median eminence: demonstration of a central role for the pituitary gland

In intact male rats the concentration of dopamine in hypophysial portal plasma of animals treated simultaneously with estradiol and progesterone was twice that of animals treated with the solvent vehicle. Treatment with estradiol or progesterone alone had no effect on dopamine in portal plasma. The rate of synthesis of dihydroxyphenylalanine (DOPA), the precursor of dopamine, in tuberoinfundibular dopaminergic (TID) neurites in the median eminence (ME) was 15 +/- 1.0 (mean +/- SE) pmol DOPA/ME.h in estradiol-progesterone-treated animals compared to 3.2 +/- 0.02 in vehicle-treated controls. Treatment with estradiol or progesterone alone gave a result similar to that seen in controls. In hypophysectomized animals treated with estradiol and progesterone, DOPA synthesis in the ME was greatly attenuated compared to that in intact rats. The in situ activity of tyrosine hydroxylase (TH; expressed as moles of DOPA per mol TH/h) in the ME was 178 +/- 16.5 in estradiol-progesterone-treated intact rats, but was 27 +/- 2.4, 52 +/- 4.2, and 35 +/- 2.5 in animals treated with the solvent vehicle, estradiol, and progesterone, respectively. In hypophysectomized rats the in situ activity of TH in the ME of animals treated with estradiol and progesterone was 53 +/- 8.4, which was significantly (P less than 0.01) less than that in similarly treated intact animals. The circulating PRL level in vehicle-treated animals was 35 +/- 4.6 ng/ml compared to 121 +/- 16 in estradiol-treated animals and 133 +/- 12.2 in estradiol- and progesterone-treated rats, indicating that the difference in the effects of estradiol and estradiol-progesterone on dopamine release, DOPA synthesis, and in situ TH activity was not solely due to a difference in circulating PRL levels. Maintenance for 7 days of anterior pituitary tissue as a graft in a lateral ventricle of intact rats resulted in a 2-fold increase in the synthesis of DOPA and TH activity in the ME compared to that in animals with liver implants. Results obtained in hypophysectomized animals with implants were similar to those in intact animals. The concentrations of PRL in cerebrospinal fluid of intact rats and hypophysectomized rats with anterior pituitary implants in the lateral ventricles were 96 +/- 32 and 127 +/- 35 ng/ml, respectively, which was significantly (P less than 0.001) greater than those in animals with liver implants. We suggest that a factor of pituitary origin stimulates TH activity in TID neurons. This stimulation may be due to PRL, but the existence of another stimulatory substance secreted by pituitary cells cannot be excluded.     

The preovulatory prolactin surge is prolonged by a progesterone-dependent dopaminergic mechanism

The preovulatory PRL surge consists of a sharp peak, a prolonged plateau, and a termination phase. This study examined the role of progesterone in maintaining elevated PRL release during the plateau phase and its effect on dopaminergic (DA) neuronal activity. Immature rats were injected with PMSG on day 28, and blood was collected during the periovulatory period. Plasma estradiol levels were elevated before and during the PRL peak and declined during the plateau. Plasma progesterone levels were low before and during the peak, rose 4- to 5-fold during the plateau, and decreased to basal levels at the termination phase. In a second experiment rats were subjected to acute ovariectomy (OVEX) or sham surgery (SHAM) just before the onset of the PRL surge. Some OVEX rats were either immediately implanted with an estradiol-containing capsule or given three injections of progesterone during the time of the plateau phase. Blood PRL levels in SHAM rats showed the typical peak, plateau, and termination phases. The PRL peak was evident, but the plateau was missing in OVEX rats with or without estradiol treatment. Replacement with progesterone restored the plateau. In a third experiment, the stalk-median eminence, posterior pituitary, and striatum were removed during the time of the midplateau phase. Tyrosine hydroxylase activity was determined in tissue homogenates by a coupled hydroxylation-decarboxylation assay. Tyrosine hydroxylase activity in the stalk-median eminence of SHAM and progesterone-treated OVEX rats was similar, but was significantly lower than that in OVEX rats with or without estradiol. Tyrosine hydroxylase activity in the posterior pituitary and striatum was unchanged. To assess the functional DA input to the anterior pituitary, haloperidol, a DA antagonist, was injected during the midplateau phase. It induced a 12- to 17-fold rise in plasma PRL in both untreated and estradiol-treated OVEX rats, but failed to increase PRL above the plateau levels in SHAM and progesterone-treated OVEX rats. We conclude that the plateau phase of the preovulatory PRL surge is dependent on the concomitant rise in progesterone. Progesterone probably acts by reducing the DA neuronal activity in the SME, resulting in an absence of functional DA input to anterior pituitary lactotrophs.     

Divergent effects of glucocorticoid on the gene expression of vasoactive intestinal peptide in the rat cerebral cortex and pituitary.

We investigated the effects of glucocorticoid on the expression of the vasoactive intestinal peptide (VIP) gene, a neuropeptide and an established prolactin (PRL)-releasing factor, in the rat brain and pituitary. The mRNA and peptide contents of VIP in the cerebral cortex, hypothalamus and anterior pituitary of male Sprague-Dawley rats were quantitated 4 weeks after adrenalectomy or sham-operation. Following adrenalectomy, VIP mRNA content increased in the anterior pituitary but showed no significant change in the cerebral cortex and hypothalamus. Dexamethasone treatment for 10 days abolished the effect of adrenalectomy and decreased significantly pituitary VIP mRNA content in sham-operated rats. In the cerebral cortex, however, dexamethasone treatment resulted in an enhancement in VIP mRNA levels in both sham-operated and adrenalectomized animals. Hypothalamic VIP mRNA content remained unchanged. These changes in VIP mRNA levels were accompanied by parallel changes in VIP concentrations in the tissues studied, suggesting that glucocorticoid regulates the synthesis of VIP in the cerebral cortex and anterior pituitary. On the other hand, serum PRL level increased after adrenalectomy but became suppressed following dexamethasone administration, in parallel with changes in pituitary VIP synthesis. These findings suggest that the effect of glucocorticoid on PRL secretion may be mediated, at least in part, via changes in VIP synthesis and secretion. We conclude that glucocorticoid regulates the expression of VIP in the rat brain, resulting in divergent changes in the cerebral cortex and pituitary. Changes in VIP synthesis and secretion may contribute to the disturbances in brain function and PRL secretion in conditions of glucocorticoid excess.     

Estriol affects prolactin and LH secretion in rats

The effects of estriol on serum prolactin (PRL) and LH levels, on the pituitary response to TRH and LHRH and on the synthesis and release of PRL from the anterior pituitary gland were investigated in female rats. The increase of serum PRL levels after estradiol administration was found to be associated with an increase of glutamic acid decarboxylase (GAD) and GABA-transaminase (GABA-T) in the hypothalamus. Thus, a study was carried out on the effects of estradiol and estriol on PRL secretion and on GAD, GABA-T and gamma-amino butyric acid (GABA) in the hypothalamus and the anterior pituitary. Under basal and TRH-stimulated conditions, estriol increased serum PRL levels, decreased basal serum LH levels, and increased the response to LHRH, in terms of LH release. Estradiol and estriol increased the synthesis and release of 3H-PRL from hemipituitary glands in incubations of pretreated animals. Both estrogens induced hyperprolactinemia, concomitantly with an increase of hypothalamic GAD and GABA-T activity. Estriol increased hypothalamic GABA concentration, but did not modify GABA concentration in the pituitary glands. Our results show that estriol, at relatively high doses, seems to be active in increasing PRL synthesis and release and in decreasing serum LH levels; it can also modify pituitary response to TRH and LHRH stimulation.     

Delta 9-tetrahydrocannabinol suppression of prolactin secretion in the rat: lack of direct pituitary effect

The effects of (--)trans-delta 9-tetrahydrocannabinol (THC) on tonic PRL secretion were investigated in long term ovariectomized or hypophysectomized/pituitary-autografted female rats and in flask incubations of anterior pituitary tissue. Intravenous injection of 0.25-8.0 mg THC/kg BW into ovariectomized rats markedly suppressed serum PRL 60 min later relative to control PRL levels. In a second experiment, ovariectomized rats bearing intraatrial cannulae were injected with 0.5 mg THC/kg BW, iv, and serial blood samples were drawn. PRL was significantly suppressed at 10 min, with persistence of the suppression for the duration of the 70-min sampling period in this time-course study. In contrast, the administration of 1.0 mg THC/kg BW, iv, to hypophysectomized/pituitary-autografted female rats failed to influence PRL secretion throughout a 120-min posttreatment sampling period. The apparent inability of THC to directly suppress PRL release from pituitary tissue was further studied by in vitro flask incubations of anterior pituitary tissue. Although a 1-h exposure of rat anterior pituitary tissue to bromocryptine (CB-154; 2.2 X 10(-4) M) suppressed subsequent PRL release, similar exposure to 10(-6) or 10(-4) M THC had no influence. The failure of THC to alter tonic PRL secretion in hypophysectomized/pituitary-autografted rts or PRL release from pituitary tissue in vitro strongly suggests that the central nervous system rather than the pituitary is the site of THC action in the acute suppression of tonic PRL secretion.     

Indirect evidence to suggest that prolactin mediates the adrenal action of haloperidol to stimulate aldosterone and corticosterone secretion in rats.

The effect of dopamine-antagonists on steroid secretion has revealed conflicting results regarding the confirmation of in vivo findings in vitro. In order to discriminate in vivo systemic and local action of the dopamine-antagonist haloperidol (HAL) on aldosterone and corticosterone secretion, microdialysis of the adrenal cortex in conscious, freely moving rats was employed. The effects of 2.5 mg HAL ip or intraadrenal dialysis of 20 micrograms/ml HAL in rats with an intact pituitary gland on PRL, aldosterone, and corticosterone secretion were examined. Systemic HAL application resulted in a 40-fold increase in PRL secretion and stimulated aldosterone and corticosterone production significantly. In contrast, intraadrenal dialysis of HAL had no effect on the secretory pattern of PRL or either steroid hormone, indicating no direct drug action on cells of the rat adrenal cortex. Similarly, ip injection of 2.5 mg HAL in hypophysectomized rats did not alter PRL or steroid hormone levels. We conclude that the dopamine-antagonist HAL stimulates aldosterone and corticosterone secretion in rats through a pituitary factor, probably PRL, but not through direct effects at the adrenal cortex.     

Dopamine transporters participate in the physiological regulation of prolactin

Three populations of hypothalamic neuroendocrine dopaminergic (NEDA) neurons, arising from the arcuate and periventricular nuclei of the hypothalamus release dopamine (DA) that acts at the pituitary gland to regulate the secretion of PRL. It is generally accepted that NEDA neurons lack functional DA transporters (DATs), which are responsible for uptake of DA from the synaptic cleft into the presynaptic axon terminal. This study localized DATs to the hypothalamo-pituitary axis and evaluated the effect of DAT blockade on the hypothalamo-pituitary regulation of PRL. After 7 days of treatment with cocaine (a nonspecific amine transporter blocker) or mazindol (a specific DAT blocker), the relative abundance of PRL messenger RNA (mRNA) in the anterior lobe (AL) of OVX rats was significantly decreased, whereas the relative abundance of tyrosine hydroxylase mRNA in the hypothalamus was significantly increased. The effect of cocaine or mazindol administration on DA turnover and serum PRL concentration was examined in estradiol (E2)-treated OVX rats. E2 administration (i.v.) resulted in a significant increase in serum PRL within 4 h; however, cocaine or mazindol administration abolished the E2-induced increase of PRL. Cocaine or mazindol significantly increased the concentration of DA at the site of the axon terminals within the median eminence (ME), intermediate lobe (IL) and neural lobe (NL), indicating blockade of uptake. Because formation of DOPAC requires uptake of DA, concentrations of DOPAC in the ME, IL and NL decreased following treatment with either cocaine or mazindol. These data, together with the presence of immunopositive DAT in the ME, pituitary stalk, IL, and NL, suggest that a functional DAT system is present within all three populations of NEDA neurons. Moreover, similarity between the effects of cocaine and mazindol treatment indicate that blockade of the DAT, but not other amine transporters, is responsible for suppression of PRL gene expression and secretion. Blockade of DATs prevent uptake of DA into NEDA neurons and consequently increases the amount of DA that diffuses into the portal vasculature and reaches the AL. These data provide evidence that DATs play a physiological role in the regulation of DA release from and TH expression in NEDA neurons and consequently PRL secretion and PRL gene expression and further support our previous observation that the regulation of PRL secretion involves all three populations of NEDA neurons.     

Absence of direct regulation of prolactin cells by estradiol-17 beta in rainbow trout (Oncorhynchus mykiss).

The effects of estradiol-17 beta (E2) implants on plasma prolactin (PRL) concentrations, pituitary PRL content and pituitary PRL mRNA levels were examined in rainbow trout (Oncorhynchus mykiss). Intact immature fish treated with 1 mg estradiol-17 beta did not show significant changes in both PRL mRNA levels and pituitary PRL content after 3 days of treatment. In a similar experiment, no changes were observed in plasma PRL levels followed during 7 days. Similarly, lack of estradiol-17 beta effect on plasma PRL levels and on final PRL pituitary content was observed in ovariectomized female rainbow trout treated during 48 days with 25 mg estradiol-17 beta and in mature male fish over a 3-week treatment period. Localization of estradiol receptor (ER) mRNAs in the pituitary was carried out by Northern blot analysis using a full-length rainbow trout estrogen receptor (rtER) cDNA as a probe. The rostral pars distalis of the pituitary which contained mostly PRL cells showed the lower amount of rtER mRNA when compared to other parts of the pituitary. Moreover, two mRNAs of different size (3.5 and 1.4 kb) were detected in different parts of the pituitary. Further hybridization experiments using probes containing part of the rtER cDNA (E domain or C and D domains) indicated that the small-sized mRNA (1.4 kb) probably encodes a truncated ER protein lacking hormone binding domain or an ER-related protein. Thus, only the 3.56 kb mRNA appeared to be involved in the regulation of pituitary function by estradiol. In situ hybridization analysis allowed a more precise localization of this rtER mRNA in the pituitary.(ABSTRACT TRUNCATED AT 250 WORDS)     

Preferential increase in pituitary prolactin versus vasoactive intestinal peptide as a function of estradiol benzoate dose in the ovariectomized rat

Vasoactive intestinal peptide (VIP) is synthesized in various tissues, including the anterior pituitary gland, where it may stimulate the release of PRL. Because estrogen plays a central role in the regulation of PRL, it becomes important to determine the effects of this steroid on both pituitary VIP and PRL. To study this, pituitary VIP and PRL and plasma PRL were assayed in ovariectomized rats after treatment with estradiol benzoate (EB; 0.007, 0.07, 0.7, 7 or 70 microgram/rat). Pituitary and plasma TSH were also determined as well as VIP content in the medial basal hypothalamus, suprachiasmatic region, cerebral cortex, and jejunum. Oil-treated rats served as controls. Injection of 0.7 or 7 microgram EB resulted in a significant increase in pituitary PRL without changing plasma PRL levels or pituitary VIP content compared to values in the control group. Only treatment with 70 microgram EB produced a significant increase in both pituitary VIP and PRL as well as in plasma PRL compared to control values. EB treatment at any of the doses used had no significant effect on pituitary and plasma TSH or VIP content in any of the other tissues examined. These data show that pituitary PRL and VIP are differentially regulated in response to estrogen. The increases in pituitary VIP and basal plasma PRL after treatment with the highest dose of EB suggest that pituitary VIP may be involved in the development of estrogen-induced hyperprolactinemia. These data also show that the regulations of pituitary VIP and TSH are independent of each other in the estrogen-treated rat.     

Melatonin effects on prolactin secretion in pituitary-grafted female rats

Melatonin influences prolactin (PRL) secretion through unknown mechanisms. This work was undertaken to study the effects of melatonin administration of PRL secretion in pituitary-grafted female rats. Melatonin administration resulted in a marked and rapid decrease of previously high plasma PRL levels in pituitary-grafted rats. Luteinizing hormone releasing hormone (LHRH) administration resulted in a marked decrease of plasma PRL levels in both sham-operated and grafted animals given saline whereas a statistically significant increase was observed in grafted, melatonin-treated rats. Estradiol benzoate administration caused an increase in plasma PRL levels of greater magnitude in the afternoon than in the morning in sham-operated animals given saline whereas in grafted animals no response to estradiol benzoate was detected. Melatonin increased the plasma PRL response to estradiol benzoate in sham-operated rats as compared to vehicle-treated animals. A normalization of PRL response to estradiol benzoate was shown in melatonin-treated, pituitary grafted rats. While the suppressive effects of melatonin in plasma PRL levels of pituitary-grafted animals is substantial the mechanism of this inhibition remains unknown.     

Correlation of rat pituitary prolactin messenger ribonucleic acid and hormone content with serum levels during the estrogen-induced surge

The model of the serum PRL surge generated in the ovariectomized rat after estradiol benzoate (EB) treatment was used to study the relationship between serum and pituitary PRL levels and pituitary PRL mRNA levels. Adult ovariectomized rats were injected sc with 7 micrograms EB or vehicle at noon on day 0. Three days later (day 3), the rats were decapitated every 4 h over a 24-h period (0800 h on day 3 to 0400 h on day 4) for determination of serum and pituitary PRL and GH levels by RIA. In addition, PRL and GH mRNA content was determined using dot blot hybridization with cDNAs. Administration of EB resulted in a significant rise in serum PRL levels at 1200, 1600, and 2000 h on day 3 compared to control values. At other times, serum PRL levels in the EB group were the same as control values. EB treatment also elicited a marked increase in pituitary PRL content at all time periods examined except during (1600 and 2000 h) and after the PRL surge (2400 h on day 3) when there was a significant reduction in stored pituitary PRL. The pituitary PRL mRNA content in the EB-treated group was significantly elevated (4- to 6-fold) over control levels throughout the study. Furthermore, PRL mRNA levels in EB-treated rats were significantly higher at 2000 and 2400 h on day 3 than at other time periods. In contrast to its effects on PRL, EB treatment had a slight inhibitory effect on pituitary GH content at 2000 and 2400 h on day 3 compared to control values; otherwise, this steroid had no effect on serum GH levels and pituitary GH mRNA content. Interestingly, serum GH levels and pituitary GH mRNA content in both treatment and control groups fluctuated in a pattern consistent with circadian rhythms, with peak values occurring during the lights-on hours. These data show that estrogen has a stimulatory effect on pituitary content of PRL and its corresponding mRNA in the rat 3 days after injection. These elevated PRL mRNa levels may be necessary for the occurrence of PRL surges. Furthermore, the facts that serum PRL levels were elevated only at certain times (1200-2000 h on day 3) while PRL mRNA content was increased at all times in the EB-treated rats suggest a differential regulation between PRL release and biosynthesis.     

The role of the suckling stimulus in regulating pituitary prolactin mRNA in the rat

Prolactin (PRL) gene expression and the synthesis and secretion of PRL were examined in ovarian-intact lactating rats suckling eight pups on 10 days postpartum. Plasma samples were assayed for PRL concentrations, and pituitary glands were analyzed for total PRL content and PRL mRNA levels. We found that suckling-induced hyperprolactinemia was associated with very high levels of plasma PRL and a doubling in pituitary PRL mRNA levels, whereas pituitary PRL content was not changed. Removal of the suckling pups decreased plasma PRL concentrations 15-fold within 24 h. This decrease in PRL secretion was not accompanied by any significant change in pituitary PRL content. Evidently, both synthesis and secretion of PRL were decreased in the pituitary gland within 24 h following cessation of suckling, as pituitary PRL mRNA content had returned to diestrous levels at this time. To determine whether or not ovarian steroids might have contributed to the changes in PRL synthesis and secretion during lactation and after withdrawal of the suckling stimulus, the experiments were repeated in lactating rats ovariectomized (OVX) on day 2 postpartum. The results in these OVX rats were qualitatively similar to those described in ovarian-intact rats. We concluded from these findings that the stimulus of suckling induces increases in PRL mRNA levels in the pituitary which provides for the increased PRL synthesis accompanying increased PRL secretion. The cessation of suckling led to prompt decreases in PRL synthesis and secretion within 24 h.     

Thyroid hormone specifically inhibits prolactin synthesis and decreases prolactin messenger ribonucleic acid levels in cultured pituitary cells

Electrophoretic analysis of soluble proteins from pituitary cells pulse labeled with [35S]methionine demonstrated that 10 nM T3 inhibited PRL synthesis, but did not affect the synthesis of most other pituitary proteins. The effects of T3 were somewhat slow, requiring about 3 days for a 50% reduction in PRL synthesis. PRL synthesis slowly returned toward control levels after the removal of T3 from the culture medium. In serum-free medium, a concentration of about 0.6 nM T3 was required for half-maximal inhibition of PRL synthesis. In medium containing 5% fetal calf serum, only slightly higher concentrations of T3 were required to inhibit PRL synthesis. The Kd for the binding of [125]T3 to pituitary cell nuclei was 0.2 nM. Analysis of PRL mRNA levels by hybridization of total cellular RNA to PRL cDNA demonstrated that there was a good correspondence between T3 effects on PRL synthesis and PRL mRNA. These findings demonstrate that T3 can specifically inhibit PRL synthesis and PRL mRNA levels in cultured pituitary cells and suggest that T3 may have a physiological role in the regulation of PRL synthesis.