Responses of the anterior pituitary of ovariectomized rats to oestradiol-17 beta administration

The response of the female rat anterior pituitary gland to oestradiol-17 beta administered sc by silastic capsule implants (6-120 microgram/day) has been examined. Cholesterol, oestradiol-17 alpha, and testosterone were used as control hormone implants. The biochemical changes in the gland as assayed by DNA, RNA, and protein contents were monitored at intervals of 7, 21, 42, and 120 days. In addition, the number of cells per gland was determined by an experimental cell counting technique and correlated to the number of cells based on total DNA content. These results extend previous observations of the hypertrophy of the anterior pituitary and show essentially parallel increases in cell number, DNA, RNA, and protein contents.     

Direct effect of estradiol on the number of dopamine receptors in the anterior pituitary of ovariectomized rats

The effect of 17 beta-estradiol (17 beta E2) on anterior pituitary dopaminergic receptor (D2) content was studied in vitro in relation to PRL secretion. Anterior pituitaries from ovariectomized rats were incubated for short periods in medium 199, with or without the steroid. Dopamine (DA) receptors in partially purified pituitary membranes were quantified by equilibrium binding using [3H]spiperone; the PRL released into the incubation medium was analyzed by RIA. Addition of 10(-10) to 10(-6) M 17 beta E2 to the incubation medium of anterior pituitaries rapidly and reversibly decreased the number of DA receptors (P less than 0.01 to 0.001), while increasing PRL release, in a dose-related fashion. The maximal effect on both receptor numbers and PRL secretion was obtained with 10(-8) M 17 beta E2. This effect involved no change in receptor affinity (Kd = 0.11 +/- 0.01 nM in presence or in absence of 17 beta E2). This estrogen-induced decrease in DA-binding capacity was apparently not the result of the occupation of spiperone binding sites by the steroid, since after a 30-min incubation with 10(-8) M [3H]17 beta E2, no radioactivity was detectable on the partially purified membranes. Moreover, the presence of 17 beta E2 at the same time as the labeled D2 ligand did not modify the kinetics of association or dissociation of spiperone with pituitary membranes. This decrease in anterior pituitary DA receptor content and the increase in PRL release were already significant after a 7-min incubation in the presence of 10(-8) M 17 beta E2. Finally, these effects of 17 beta E2 were not mimicked by its 17 alpha-stereoisomer, nor by progesterone, or testosterone. These results suggest that the stimulatory effect of 17 beta E2 on PRL secretion may be due, at least in part, to the desensitization of anterior pituitary cells to DA. The steroid may produce this desensitization directly by decreasing the number of D2. The short latency of this effect likely discards the possibility of a genomic action of 17 beta E2.     

Effects of catecholestrogens on luteinizing hormone levels in long tem ovariectomized adult rats

The long term ovariectomized adult rat was used to test the effects of exogenous estradiol, 4-hydroxyestradiol, and 2-hydroxyestradiol on LH secretion. To this end, different doses of estradiol 3-benzoate, 4-hydroxyestradiol 3,4-dibenzoate, and 2-hydroxyestradiol 2,3-dibenzoate were injected daily at 0800 h, and the LH serum levels were measured on 4 experimental days. At a dose of 1 micrograms/day, estradiol benzoate lowered LH secretion, beginning 48 h after the first injection (morning of day 2), and induced a characteristic LH surge 10 h later. 4-Hydroxyestradiol dibenzoate at the same dose produced less suppression of LH on the morning of day 3, but caused a comparable and highly significant surge on the same evening. Higher doses (3 and 10 micrograms/day) resulted in the same pattern seen with estradiol benzoate. 2-Hydroxyestradiol dibenzoate at comparable doses had no effect. Only extremely high doses (129 micrograms/day) caused slight suppression of tonic LH secretion 72 h after the first injection, and inconsistent LH elevations occurred on the same evening. It is concluded that in this model, catecholestrogens act as estrogens with respect to LH suppression and release, with 4-hydroxyestradiol being a potent estrogen and 2-hydroxyestradiol a weak estrogen.     

Effects of thyroxine on oestrogen receptor concentrations in anterior pituitary and hypothalamus of hypothyroid rats

The effects of thyroxine (T4) were studied on the concentration of oestrogen receptors in the anterior pituitary gland and hypothalamus of ovariectomized euthyroid and hypothyroid rats. A group of rats was made hypothyroid by the administration of 131I. Seven days after ovariectomy, animals were separated into five groups: I, euthyroid controls; II, hypothyroid controls; III, hypothyroid and injected with oestradiol benzoate (10 micrograms/day for 10 days); IV, hypothyroid and injected with T4 (4 micrograms/day for 10 days) and V, hypothyroid and injected with both oestradiol and T4 as described above. In group I, oestrogen receptor levels in pituitary cytosol were 44.4 +/- 3.4 (S.D.) fmol/mg protein and in the nucleus 47.7 +/- 4.0 fmol/mg DNA. In group II the respective values were 12.8 +/- 1.7 fmol/mg protein (P less than 0.01) and 12.7 +/- 1.7 fmol/mg DNA (P less than 0.01 compared with group I). In group III, cytosolic receptor concentrations decreased when compared with those in group II (P less than 0.05), whereas nuclear receptor concentrations rose significantly (P less than 0.01). Group IV had both pituitary cytosolic and nuclear receptors increased (P less than 0.01 compared with group II). In group V there were no changes in cytosolic receptor concentrations but a significant (P less than 0.01) rise in nuclear receptors as compared with group II. Hypothalamic oestrogen receptors in untreated hypothyroid rats (group II) were unchanged in the cytosol and diminished (P less than 0.01) in the nucleus in relation to euthyroid controls (group I). Thyroxine, but not oestrogen, was effective in increasing the concentration of cytosolic receptors (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of estrogen-induced hyperprolactinemia on endocrine and sexual functions in adult male rats

Chronic estrogen treatment can lead to development of prolactin (PRL) secreting pituitary tumors. We have tested the ability of diethylstilbestrol (DES) to produce persistent hyperprolactinemia (hyperPRL) in adult male rats and examined the effects of this treatment on hypothalamic-pituitary-testicular function, adenohypophyseal structure, copulatory behavior and fertility. Silastic capsules containing approximately 5 mg DES were subcutaneously implanted into adult male CDF (F-344)/CrlBR rats and removed 15 or 20 weeks later. Extreme hyperPRL, as well as suppression of plasma LH and FSH levels, persisted after DES capsules were removed. In contrast, plasma testosterone levels increased rapidly after removal of DES capsules and reached normal levels within 4-6 weeks. Copulatory behavior was assessed on two occasions between 7 and 14 weeks after removal of the DES capsules and was found to be suppressed in DES-treated rats, as evidenced by significant increases in latencies to mount, to intromit and to ejaculate. Moreover, when the animals were placed with normal females, the interval until conception was significantly greater in DES-treated than in control males. In spite of these differences in copulatory behavior, 10 of 11 DES-treated males were fertile. At autopsy, 44 weeks after capsule implantation (i.e. 24 or 29 weeks after capsule removal), DES-treated rats had marked enlargement of the anterior pituitary, increased weights of the lateral prostate and the adrenals, increased levels of testicular hCG-binding sites, reduced concentration of dopamine and norepinephrine in the median eminence and increased concentration of LHRH in the preoptic area.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prolactin release, oestrogens and proliferation of prolactin-secreting cells in the anterior pituitary gland of adult male rats

Relationships among the release of prolactin, the effect of oestrogens and the proliferation of prolactin-secreting cells were studied under several experimental conditions. Administration of sulpiride or oestradiol released prolactin and stimulated cell proliferation in the anterior pituitary gland of adult male rats. Clomiphene completely abolished the rise in cell proliferation, but did not interfere with the sulpiride-induced release of prolactin. Treatment with oestradiol plus sulpiride significantly increased serum prolactin concentrations and the mitotic index compared with the sum of the stimulation produced by both drugs separately. Bromocriptine abolished the stimulatory effect of oestradiol on the serum prolactin concentration and on cell proliferation. In oestradiol- and/or sulpiride-treated rats, 80% of the cells in mitoses were lactotrophs. The remaining 20% did not stain with antisera against any of the pituitary hormones. The number of prolactin-secreting cells in the anterior pituitary gland significantly increased after the administration of oestradiol or sulpiride. The results demonstrate that treatment with sulpiride and/or oestradiol increases the proliferation and the number of lactotrophs in the anterior pituitary gland of the rat.     

斑蝥黄质抗去势雌性大鼠骨质疏松的实验研究

目的 探讨斑蝥黄质对去卵巢骨质疏松(OP)模型大鼠股骨的密度、骨矿含量的影响及机制.方法 将72只15周龄SD大鼠随机分为6组,空白组行假手术,其余5组行卵巢切除术,术后用药12 w后处死,测定右侧股骨骨密度、骨矿含量、血清雌二醇(E_2)、碱性磷酸酶(ALP)含量及子宫湿重.结果 与模型组相比,斑蝥黄质高(20 mg/kg)、中(15 mg/kg)、低剂量(10 mg/kg)组和尼尔雌醇组(1.05 mg/kg)能缓解因去势后造成的雌鼠骨密度、骨矿含量、血清E_2及子宫指数的下降(P＜0.05),同时可以抑制血清ALP水平的升高(P＜0.05).结论 斑蝥黄质可以改善骨质量,抑制雌性大鼠去卵巢OP的发生,可能具有类似雌激素的效应.     

葛根素对去卵巢大鼠机体骨代谢影响的观察

目的 观察葛根素对去卵巢大鼠机体骨代谢的影响,探讨其对雌激素缺乏引起的骨质疏松症的治疗作用.方法 3月龄清洁级SD大鼠60只,背驮式切除双侧卵巢后每日灌胃葛根素5 mg/kg(P-5组),10 mg/kg(P-10组)和20 mg/kg(P-20组),并设假手术组(Sham),模型组(OVX)和己烯雌酚阳性对照组(E).3个月后处死动物,测定大鼠胫骨干重、灰分重量和矿物质含量,胫骨Ca、P含量以及血清相关骨代谢指标.结果 与OVX组相比,葛根素各组的胫骨矿物质含量(mg/g)均有增加(574±17,590±22和597±18),其中P-20组差异显著(P＜0.05);葛根素各组的胫骨Ca含量(mg/g)高于OVX组 (132±10,222±7,228±8),其中P-10,P-20两组差异显著(P＜0.05,P＜0.01),说明服用葛根素后大鼠骨量得到增加;同时,葛根素各组的碱性磷酸酶(U/L)与OVX组有所降低(101±26,90±20,71±15),其中P-10,P-20两组差异显著(P＜0.05,P＜0.01),说明去卵巢大鼠骨的高转换状态得到改善.结论 葛根素能抑制去卵巢大鼠骨量的丢失,对骨代谢有较好的调节作用,对雌激素缺乏引起的骨质疏松症有一定的治疗作用.     

Estrogens decrease expression of the corticotropin-releasing factor gene in the hypothalamic paraventricular nucleus and of the proopiomelanocortin gene in the anterior pituitary of ovariectomized rats

It is known that estrogens modulate the hypothalamopituitary—adrenal (HPA) axis both under resting conditions and during exposure to stress. Nevertheless, the site of action of estrogens is not still fully elucidated. We sought to determine if estrogens could act on the major hypothalamic ACTH secretagogue: corticotropin-releasing factor (CRF). Mature rats were ovariectomized (OVX) and 2 weeks later implanted with silastic capsules containing 17β-estradiol (E₂). Animals were sacrificed 7 days later. CRF mRNA in the hypothalamic paraventricular nucleus (PVN) and proopiomelanocortin (POMC) mRNA in the anterior pituitary were measured byin situ hybridization. CRF content in the median eminence was measured by semiquantitative immunocytochemistry. E₂ treatment induced a significant decrease of CRF mRNA levels in the PVN (3.70±0.14vs 4.79±0.15 copies of probe×10⁻³/μm³ of tissue in OVX rats,P<0.05), an accumulation of immunoreactive CRF in the zona externa of the median eminence (207±36vs 100±15% in OVX rats,P<0.05), and a decrease of POMC mRNA levels in the anterior pituitary (4.6±0.6vs 6.9±0.6 copies of probe ×10⁻²/μm³ of tissue in OVX rats,P<0.05). These results demonstrate that estrogens have a negative effect on CRF gene expression and secretion and on POMC gene expression. Whether estrogens modulate directly the CRF-synthesizing cells or act through an increase of the glucocorticoid negative feedback remains to be determined.     

PR localization and anterior pituitary cell populations in vitro in ovariectomized wild-type and PR-knockout mice

The PR is critical for normal female reproductive function in mammals, including primates, and the PR-knockout mouse is an important model for establishing PR targets. For example, LH secretion is significantly altered both in vivo and in vitro in female PR-knockout mice, but to establish specific mechanisms affected by the absence of the PR in the mouse requires characterization of wild-type mouse cell biology. As steps toward this, the aims were to establish whether altered LH secretion in PR-knockout mice reflects altered mouse gonadotrope cell lineage during development secondary to PR deletion and to test the assumption that PR in wild-type mouse pituitaries has the same exclusive gonadotrope localization and E2 and progesterone regulation as in rat and monkey pituitaries. As an in vitro model, dispersed pituitary cells from 2-wk ovariectomized wild-type or PR-knockout mice were cultured +/- E2 for 3 d. These cells were subjected to dual immunofluorescence staining for PR and LH, PRL, or GH. The proportion of LH-gonadotropes (8-9%) and somatotropes (26-29%) was not different for PR-knockout and wild-type cultures with or without E2. Lactotrope composition (41-42%) was the same in wild-type and PR-knockout, and E2 resulted in a similar and significant increase in the proportion (57-59%) for both mouse types. Nuclear PR immunoreactivity was absent in all PR-knockout pituitary cells. For wild-type, all LH gonadotropes showed nuclear PR immunoreactivity that was up-regulated by E2 (>10-fold increase). Progesterone exposure for 10 h but not 3 h led to a 40% decrease in PR immunoreactivity in LH-gonadotropes. Unexpectedly, PR immunoreactivity also localized to all lactotropes and was up-regulated by E2 and down-regulated by progesterone. In summary, the absence of PR has no effect on the proportion of LH gonadotropes, lactotropes, and somatotropes in ovariectomized PR-knockout mouse pituitary cultures. For ovariectomized wild-type mice, gonadotropes in the in vitro model contain PR that is up-regulated by E2, but the downregulation by progesterone is modest, compared with that previously reported for an in vitro rat model. In contrast to rats and monkeys, E2-dependent PR also is present in lactotropes of ovariectomized wild-type mice. These results underscore the risks in assuming identical cell biology between rats and mice.     

Effect of neonatal and adult testosterone treatment on the cellular composition of the adult female rat anterior pituitary

The adult female pituitary has significantly more lactotrophs than that of the male, while the later has a higher percent of somatotrophs. It is clear that GH and prolactin (PRL) gene expression and somatotroph and lactotroph proliferation are modulated by the postpubertal hormone environment; however, the role of the neonatal steroid environment in this process is not known. We have used in situ hybridization to determine the number of GH and PRL mRNA-containing cells, as well as the level of expression of these two hormones, in response to neonatal and adult testosterone treatment. Female rats exposed to testosterone during the neonatal period, adulthood or both periods, as well as normal females and males were used. Exposure to testosterone during the neonatal period significantly increased the percentage of somatotrophs (ANOVA: P<0. 005) and decreased that of lactotrophs in the adult female rat (ANOVA: P<0.001). Adult testosterone treatment had no significant effect on the percentage of somatotrophs. The percentage of lactotrophs was significantly increased by adult testosterone only in those rats also exposed to neonatal testosterone. PRL mRNA concentrations, as reflected by silver grains/cell, were reduced by neonatal testosterone and increased by adult testosterone treatment (ANOVA: P<0.0001). Overall PRL mRNA levels, measured by densitometry, were also reduced by neonatal testosterone exposure, but adult testosterone had no effect (ANOVA: P<0.001). GH mRNA levels per cell, as reflected by silver grains/cell, were increased by adult testosterone, while neonatal testosterone treatment had no effect. Overall GH mRNA levels per unit area, determined by densitometry measurements, were increased by both neonatal and adult testosterone treatment, with the combination of these two treatments resulting in adult females having levels indistinguishable from intact males (ANOVA: P<0.003). These results suggest that, in combination with postpubertal sex steroids, the neonatal gonadal steroid environment plays an important role in determining anterior pituitary hormone synthesis and cellular composition.     

Kaempferol has osteogenic effect in ovariectomized adult Sprague-Dawley rats

Kaempferol (K), a flavonol, is known to have anti-osteoclastogenic effect. We here show that K, from 0.2 to 5.0 microM, increased mineralized nodules in rat primary osteoblasts. K also significantly attenuated adipocyte formation from bone marrow cells (BMCs). A single oral dose of 1 mg/kg body weight of K in Sprague-Dawley (180-200 g) rats resulted in a peak serum level of 2.04+/-0.8 nM in 30 min (Tmax), suggesting its rapid absorption. The Cmax of K in bone marrow was 0.684 nM after 90 min. Rats were ovariectomized (OVx) along with sham-operated rats and left for 4 weeks. Daily oral administration of K (5 mg/kg body weight) was then started to one group of OVx rats, and continued for 10 weeks. K levels were found to be 0.311 and 0.838 nM at the end of 4 and 10 weeks, respectively. K exhibited no estrogenicity at the uterine level. The K-treated group exhibited significantly higher bone mineral density (BMD) in the trabecular regions (femur neck, proximal tibia and vertebrae) and lower serum ALP (bone turnover marker) compared with the OVx rats. The compressive energy of the vertebrae was significantly higher in the OVx+K-treated group compared with the OVx group. K treatment of OVx rats resulted in the increase in osteoprogenitor cells as well as inhibition of adipocyte differentiation from BMCs compared with the OVx group. Together we show that K is non-estrogenic in vivo and exerts bone anabolic activity with attendant inhibition of bone marrow adipogenesis.     

铁调素对去卵巢大鼠骨代谢的影响

目的观察铁调素对去卵巢大鼠骨代谢的影响。方法将30只10周龄雌性Wistar大鼠分为假手术(sham)组、铁调素(hepc)组和生理盐水对照(OVX)组,每组10只。Hepc和OVX组行双侧卵巢摘除术后,分别经腹腔注射750μg/kg铁调素(hepcidin)溶液和等量生理盐水。9周后经颈静脉取血、处死后留股骨。检测股骨骨密度(BMD)、骨生物力学、血清骨代谢标志物及血清铁水平。结果与sham组相比,OVX组BMD及骨最大载荷、弯曲应力、弹性载荷、弹性模量均降低,差异均有统计学意义(P0.05),同时血清骨形成蛋白-2水平下降,而骨吸收指标Ⅰ型胶原交联C端肽(CTX-1)水平上升,血清铁浓度升高,差异均有统计学意义(P0.05);经铁调素干预的hepc组骨密度较OVX组增加了21.7%,上述骨生物力学指标也有明显改善,差异均有统计学意义(P0.05),虽然血清骨形成蛋白-2水平无明显升高,差异无统计学意义,但血清CTX-1水平下降33.5%,血清铁浓度降低17.2%,差异均有统计学意义(P0.05)。结论铁调素能改善绝经后骨质疏松大鼠模型骨代谢和力学特性,该作用可能通过改善体内铁超载、降低骨吸收实现。     

Cell-type specific messenger functions of extracellular calcium in the anterior pituitary.

Calcium can serve not only as an intracellular messenger, but also as an extracellular messenger controlling the gating properties of plasma membrane channels and acting as an agonist for G protein-coupled Ca(2+)-sensing receptors. Here we studied the potential extracellular messenger functions of this ion in anterior pituitary cells. Depletion and repletion of the extracellular Ca(2+) concentration ([Ca(2+)]e) induced transient elevations in the intracellular Ca(2+) concentration ([Ca(2+)]i), and elevations in [Ca(2+)]e above physiological levels decreased [Ca(2+)]i in somatotrophs and lactotrophs, but not in gonadotrophs. The amplitudes and duration of [Ca(2+)]i responses depended on the [Ca(2+)]e and its rate of change, which resulted exclusively from modulation of spontaneous voltage-gated Ca(2+) influx. Changes in [Ca(2+)]e also affected GH and PRL secretion. The PRL secretory profiles paralleled the [Ca(2+)]i profiles in lactotrophs, whereas GH secretion was also stimulated by [Ca(2+)]e independently of the status of voltage-gated Ca(2+) influx. [Ca(2+)]e modulated GH secretion in a dose-dependent manner, with EC(50) values of 0.75 and 2.25 mM and minimum secretion at about 1.5 mM. In a parallel experiment, cAMP accumulation progressively increased with elevation of [Ca(2+)]e, whereas inositol phosphate levels were not affected. These results indicate the cell type-specific role of [Ca(2+)]e in the control of Ca(2+) signaling and secretion.     

Quantification of vasoactive intestinal peptide immunoreactivity in the anterior pituitary glands of intact male and female, ovariectomized, and estradiol benzoate-treated rats.

There are considerable data suggesting that vasoactive intestinal peptide (VIP) is involved in the regulation of PRL secretion; however, the role and cell of origin of anterior pituitary VIP remain to be determined. Immunocytochemical (ICC) studies have generally failed to detect VIP-immunoreactive (IR) cells in the pituitary of the untreated rat, although VIP-IR cells have been observed in the pituitaries of hypothyroid or estrogen-treated rats. This study was designed to examine the cellular distribution and tissue content of VIP in the anterior pituitary gland of rats under selected endocrine conditions known to alter the rates of PRL and VIP synthesis and secretion. To this end, anterior pituitary VIP and PRL content (ICC and RIA) and serum PRL levels were determined in ovariectomized (OVX) and OVX rats 3 days after treatment with 7 or 70 micrograms estradiol benzoate (EB). For comparison, pituitary VIP and PRL content (ICC and RIA) and serum PRL levels in untreated male and diestrous female rats were determined. Immunostaining for VIP was accomplished using a newly developed primary antiserum. Significant numbers of VIP-IR cells per 5-microns section were found in the anterior pituitary glands of all animals examined (275 +/- 33 in diestrous to 481 +/- 103 cells in male rats). VIP was not colocalized with PRL in any of the pituitaries regardless of steroid treatment or sex. Furthermore, the number of VIP-IR cells per pituitary gland was not significantly correlated with sex or EB treatment. Treatment with 70 micrograms, but not 7 micrograms, EB significantly increased the pituitary content of VIP and serum PRL levels compared to those after ovariectomy. However, both EB treatments resulted in a significant increase in pituitary PRL content compared to that in untreated OVX rats. Pituitaries from male rats had several-fold more VIP and less PRL content than pituitaries from diestrous rats. These data show that 1) in contrast to previous ICC studies, VIP-IR cells are readily detected in the anterior pituitary of intact male and female and OVX as well as EB-treated rats; 2) VIP is localized to cells other than lactotrophs, regardless of the steroid background; and 3) marked changes in anterior pituitary VIP content are not accompanied by changes in VIP-IR cell number.     

Immunomodulation in rats by transplantable anterior pituitary tumors

The effect on the immune response of the MtT/W5 (W5), MtT/W10 (W10) tumors of Wistar-Furth rats and of MtT/F4 (F4) tumor transplantable in Fischer 344 rats was examined. Antibody response to sheep red blood cells and contact sensitivity reactions to dinitrochlorobenzene (DNCB) were used as immune parameters. In intact rats the W5 tumor suppressed the antibody response as much as did hypophysectomy (Hypox). The antibody response of Hypox rats was marginally improved by this tumor. Contact sensitivity was not suppressed in intact animals and the poor reactivity of Hypox rats was reconstituted to normal levels by W5. Treatment with bromocriptine (BRC) had no influence on tumor growth or on the immune reactivity of tumor-bearing hosts. The W10 tumor suppressed antibody formation, but not contact sensitivity in intact animals; the antibody and the DNCB response of Hypox animals was reconstituted partially, by this tumor. BRC treatment of tumor-bearing animals mimicked the effect of Hypox in this system. The F4 tumor suppressed antibody formation in intact rats and did not reconstitute the reactivity of Hypox rats. The DNCB response was not influenced by this tumor in intact animals and it was partially reconstituted in Hypox rats. Again, the reactivity of BRC-treated animals was similar to that of Hypox tumor-bearing animals. These results indicate that pituitary tumors may alter the immune reactivity of their hosts significantly.     

Dopaminergic stimulation of pituitary but not hypothalamic estrogen receptors in ovariectomized rats

This study was designed to examine the role of catecholamines and serotonin in the regulation of estrogen receptors (ER) in the medial basal hypothalamus (MBH) and anterior pituitary gland (AP) of adult ovariectomized rats. Plasma PRL and LH were also determined. Injection of alpha-methyl tyrosine (alpha-MT) resulted in the significant reduction of norepinephrine and dopamine (DA) content in the MBH, and of plasma LH levels as well as in the significant elevation of plasma PRL levels. This treatment also resulted in the significant reduction of ER concentration in the AP. The elevation in plasma PRL by alpha-MT was reversed by the simultaneous injection of bromocriptine (BC), a DA agonist, which also partially reversed the alpha-MT reduction of ER concentrations in the AP. BC had no effect on plasma LH levels. The ER concentration in the MBH was not significantly changed by any of these treatments. The reduction of serotonin content in the MBH by the injection of p-chlorophenylalanine had no effect on the ER concentration in either the MBH or AP, nor did it have any effect on plasma PRL levels. However, p-chlorophenylalanine treatment did decrease plasma LH levels. Neonatal treatment of female rats with monosodium glutamate which has been reported to destroy part of the MBH, resulted in a significant reduction in body and pituitary weight and in a significant elevation of plasma PRL levels in adults (2 months old). This treatment also resulted in a significant reduction in the AP and MBH ER concentration. Injection of BC to adults reversed the effects of neonatal monosodium glutamate treatment on plasma PRL levels and on the pituitary ER concentration, but had no effect on the ER concentration in the MBH. BC had no effect on the AP or MBH ER concentration in control rats, although it did as expected reduce the plasma PRL levels in these animals. Plasma LH levels were not significantly changed by any of these treatments. Injection of the DA antagonist, haloperidol, to adult rats resulted in a significant elevation of plasma PRL and in a significant reduction of ER concentration in the AP. Haloperidol treatment did not affect the binding affinity of these receptors. Overall, these data suggest that DA is involved with the regulation of ER in the AP.