Intrahypothalamic pituitary grafts elevate prolactin in the cerebrospinal fluid and attenuate prolactin release following ether stress

Anterior pituitary (AP) tissue grafted into the hypothalamus of female rats inhibits the luteotrophic prolactin (PRL) secretion which normally follows mating. Dopamine blockade has been shown to overcome this inhibition, suggesting that the grafts suppress PRL release from the in situ pituitary by the action of graft PRL increasing dopamine activity in the hypothalamus. To examine whether PRL levels in the cerebrospinal fluid (CSF) were elevated by the AP grafts, CSF samples were taken from 5 control rats and 10 rats bearing intrahypothalamic AP grafts. Mean PRL concentrations in the CSF of the control rats were 3.0 +/- 0.8 ng/ml. The grafted rats had significantly higher concentrations of PRL in their CSF, averaging 23.2 +/- 4.2 ng/ml (P less than 0.005). Plasma PRL concentrations were similar in the control and grafted rats. PRL release in response to 5 min of ether stress was examined in 8 control and 11 grafted rats. In control animals, PRL rose from 4.2 +/- 1.5 to 44.7 +/- 9.0 ng/ml following exposure to ether, but the response was significantly attenuated in the grafted rats, peaking at 9.3 +/- 1.4 ng/ml (P less than 0.001). This inhibition of response due to the grafts was evident within 1 week of graft placement. The results confirm that the presence of intrahypothalamic AP grafts led to the accumulation of supranormal PRL concentrations in the CSF. This elevated PRL suppressed pituitary PRL release in response to ether stress, probably by an autoregulatory feedback activation of the inhibitory tuberoinfundibular dopaminergic neurons in the hypothalamus.     

The inhibition of prolactin secretion due to intrahypothalamic pituitary grafts is reversed by estradiol benzoate but not by progesterone

Anterior pituitary (AP) tissue grafted into the hypothalamus inhibited the luteotrophic response to mating and prevented pseudopregnancy (PSP) and pregnancy. All normal rats given 10 micrograms estradiol benzoate (EB) on estrus became PSP (15 days) while the same treatment caused 10-day PSPs in 20/21 grafted rats. Doses of 30 micrograms EB or 10 micrograms EB plus reserpine (1 mg/kg) resulted in 15-day PSP in grafted rats. By contrast progesterone (P; 10 mg on estrus) did not prolong cycles in rats with hypothalamic grafts though it did in 50% of normals. Earlier studies showed that PSP or pregnancy was restored in the grafted rats by blockade of dopamine (DA) secretion. The results above show that EB was similarly effective in restoring PSP while P was not, suggesting that EB both raised prolactin and lowered DA while P was unable to lower DA in rats with AP grafts in the hypothalamus.     

Effects of estradiol on circulating levels of prolactin in female rats bearing ectopic pituitaries

The existence of local mechanisms controlling the prolactin (PRL) release from anterior pituitaries (AP) grafted to an ectopic location has been recently described. To study if these mechanisms are affected by estrogens, pituitary-grafted (GRAFT) and sham-operated (SHAM) rats were injected with a single dose of estradiol benzoate (EB), their plasma PRL levels as well as their hypothalamic and AP contents of norepinephrine (NE) and dopamine (DA) being analyzed. Administration of EB to GRAFT animals produced a small increase in their previously high plasma PRL levels, with both an increased NE and a decreased DA content in the ectopic AP. Since NE enhances the PRL release from ectopic AP and DA partially inhibits this secretion these changes may explain such a small increase in PRL levels. However, an additional increase in the decreased PRL release from the in situ AP of these animals cannot be discarded since EB produced also a decrease of the DA content in this tissue with an unaltered hypothalamic content. Finally, administration of this steroid to SHAM animals produced an important increase in plasma PRL levels. Since this increase was correlative to a decrease in DA and NE hypothalamic contents and unaltered AP contents. EB may be supposed to be able to reduce the DA synthesis in the tuberoinfundibular neurons, while the changes in noradrenergic inputs could be more related to the feedback effects of estrogens on the gonadotrophin release.     

Effect of experimentally induced hyperprolactinemia on growth hormone secretion

In order to study the existence of possible interrelation-ships between prolactin (PRL) and growth hormone (GH) secretions, adult male rats bearing an anterior pituitary graft under the kidney capsule since day 90 of life and their sham-operated controls were submitted to a single i.p. administration of L-dopa (50 mg/kg weight) or saline 30 days after the operation. Plasma PRL and GH levels were measured by using specific RIA methods. Dopamine (DA) and norepinephrine (NE) contents in the hypothalamus and in the in situ anterior pituitary gland were measured by using a specific radioenzymatic assay. An increase in plasma PRL levels and a decrease in plasma GH levels were shown in grafted rats. Hypothalamic contents of DA and NE were increased in these animals, while the anterior pituitary content of DA was not modified as compared to controls. The administration of a single injection of L-dopa led to decreases of plasma PRL and GH levels in both grafted and control rats, but while marked increases in hypothalamic and anterior pituitary contents of DA were shown in both groups, the hypothalamic content of NE was only increased in control animals. These data suggest that PRL and GH secretions were closely related. Dopamine could be mediating the action of PRL on GH, while NE would be less involved.     

Increased serum prolactin levels mediate the suppressive effects of ectopic pituitary grafts on copulatory behavior in male rats

To determine if deficits in sexual activity observed in pituitary-grafted male rats are due to elevated serum prolactin (PRL) levels found in these animals, the effects of whole pituitary grafts, pars distalis grafts, and ovine (o) PRL treatment on male copulatory behavior were compared. Adult sexually experienced CDF male rats were given four whole pituitary grafts, four pars distalis grafts, or were sham operated. Both groups of grafted animals exhibited suppressed copulatory behavior patterns when tested 18 days after pituitary transplantation. Animals given whole pituitary grafts had significantly longer latencies to mount (P less than 0.05) and to intromit (P less than 0.01) than did the sham-operated controls, while the animals given anterior pituitary grafts differed from the sham-operated controls in latencies to mount (P less than 0.05) and to intromit (P less than 0.01), as well as in the number of intromissions (P less than 0.05). Prolactin-injected animals had significantly reduced intromission rates (P less than 0.01) and significantly increased latencies to mount (P less than 0.05) and to intromit (P less than 0.01) when compared to vehicle-injected controls. Furthermore, the time course of behavioral suppression was similar in oPRL-treated animals to that observed in pars distalis-grafted males, with both groups showing the onset of deficits in sexual activity within 8 to 9 days from the induction of the hyperprolactinemic state. The similarity in pattern and time to onset of behavioral suppression in pituitary-grafted and oPRL-treated animals suggests that behavioral deficits observed in animals with pituitary grafts result from chronic elevation of serum PRL levels.     

Bromocryptine prevents the decline in tuberoinfundibular neuronal release of dopamine after removal of chronic estrogen treatment

Prolonged exposure to estradiol 17-beta (E2) in rats has been shown to decrease dopamine (DA) synthesis in and release from tuberoinfundibular dopaminergic (TIDA) neurons in Fischer 344 rats. The objective of the present study was to determine whether inhibition of the E2-induced increase in anterior pituitary (AP) weight and prolactin (PRL) secretion by concomitant administration of the dopaminergic agonist, bromocryptine, could prevent the decrease in TIDA neuronal function produced by chronic E2 administration. TIDA neuronal function was evaluated by in vitro superfusion and electrical stimulation of median eminence (ME) tissue after allowing for accumulation of [3H]dopamine (DA). The effect of chronic E2 and/or bromocryptine treatment on catecholamine content in tuberohypophyseal neurons in the neurointermediate lobe was also measured to determine whether increased pituitary size possibly damaged the tuberohypophyseal neurons. Treatment with E2 for 30 days significantly increased AP weight, serum PRL concentration, and AP PRL and DNA content over values in non-E2-treated controls. When bromocryptine was injected daily during E2 treatment, bromocryptine completely inhibited the E2-induced increase in serum PRL and AP DNA content, and AP weight was only moderately increased. The evoked release of 3H at the end of the 30-day E2 treatment was reduced during electrical stimulation and there was no augmented release of 3H from the ME tissue after 10 microM nomifensine infusion in E2-treated rats and in rats given both bromocryptine and E2. However, neurointermediate lobe DA content was diminished only in E2-treated rats and not in animals given bromocryptine together with E2. When all treatments were discontinued for 30 days, animals previously given only E2 showed sustained increases in AP weight, serum PRL levels, and AP PRL and DNA content, but reduced stimulation-evoked release of 3H, absence of response to nomifensine, and reduced neurointermediate lobe DA and norepinephrine content when compared with values in non-E2-treated controls. After withdrawal of E2 treatment for 30 days, animals previously given bromocryptine and E2 together were not different from control animals in any of the parameters measured. These results suggest that the decline in TIDA neuronal release of DA induced by chronic E2 treatment was at least partly exerted via the marked hyperprolactinemia and/or by compression of the medial basal hypothalamus by the enlarged AP.     

Enzymatic differentiation of arterial and venous segments of the capillary bed during the development of free muscle grafts in the rat

The revascularization of freely grafted muscles in the rat was studied by histochemical reactions that on frozen sections stain the arterial part of the capillary bed blue (alkaline phosphatase [AP] reaction) and the venous part of the capillary bed red (dipeptidyl peptidase IV [DPP IV] reaction). In 112 rats the extensor digitorum longus or soleus muscles were freely grafted and removed at various times up to 93 days following the surgery. In cross section, the capillaries of a normal muscle show a mosaic pattern of staining for the activity of the two enzymes. After grafting, DPP IV activity of capillaries is lost throughout the entire graft within a day or two; but within ischemic muscle, weak and diffuse AP staining persists in capillary remnants for up to 6 days. In the very periphery of the graft AP staining is also preserved in partially damaged capillaries. By 4 days, new AP-positive capillaries can be identified at the periphery of the graft, and in succeeding days AP-positive capillaries are found progressively nearer the center of the graft. At 7 days, the capillary/muscle-fiber ratios are 66% of normal in the periphery of the graft and 44% in the intermediate zone. DPP IV-stained capillaries are not seen until 7 days after grafting. By 60 days, when the grafts have become stabilized, the mosaic pattern of capillary staining has become reestablished. In mature grafts, the number of capillaries per unit area was slightly higher than that in control muscles, but the capillary/muscle-fiber ratio was slightly lower, owing to the smaller than normal cross-sectional areas of the regenerated muscle fibers.     

Ovariectomized Sprague-Dawley and Long-Evans rats release prolactin differently in response to estrogen

Mature female Sprague-Dawley (SD) and Long-Evans (LE) rats were ovariectomized (OVX), fitted with indwelling atrial catheters and given a single sc injection of either 25 or 100 μg polyestradiol phosphate (PEP); seven days later blood samples were withdrawn at two hour intervals from 1100 to 2100 hours to detect the presence of an afternoon surge of prolactin (PRL). Other groups of OVX rats of both strains also treated with PEP and catheterized as above were sampled before and at 2, 5, 10 and 30 min after iv administration of 1 μg synthetic thyrotropin releasing hormone (TRH). Pituitary (AP) and uterine weights were determined following sacrifice one day after TRH treatment. Separate groups of OVX rats of both strains treated with 100 μg PEP were decapitated 7 days later and each AP was removed and homogenized. The AP homogenates and plasma samples were assayed for PRL by radioimmunoassay. Rats of both strains had afternoon PRL surges and in both strains the magnitude and/or duration of the surges were enhanced by the higher dose of PEP. However, within each PEP dose LE rats released significantly more PRL during the surge than did SD rats. Rats of both strains also released PRL in response to TRH and this response was enhanced in both strains by the higher of the two doses of PEP. However, there were no differences between the strains at 25 μg PEP and at 100 μg PEP SD rats released significantly more PRL to TRH than did LE rats. Pituitary weight and PRL concentration were not different between the strains at either dose of PEP but LE rats had significantly heavier uteri at both doses of PEP compared to SD rats. These data not only show that strain differences exist in estrogen-induced or mediated PRL release in the rat but also indicate that the differences are not uniform. This latter observation suggests that the estrogen-induced mechanisms examined in this study are for the most part independent of each other.     

Extrahypothalamic control of daily surges of prolactin secretion in pseudopregnant rat

The role of the limbic forebrain structures in controlling twice daily surges of prolactin (PRL) induced by cervical stimulation was investigated after acute or chronic deafferentation of the limbic forebrain afferents to the hypothalamus in rats. The preoptic area-roof section (POA-RS), which interrupted the rostral limbic afferents at the dorsal level of the anterior commissure, induced pseudopregnancy (PSP) and initiated the same nocturnal PRL surges as those initiated by the cervical stimulation. Diurnal PRL surges, however, did not occur following this procedure. The nocturnal PRL surge by POA-RS also occurred in ovariectomized rats. Deafferentation between the diagonal band of Broca and the medial preoptic area (F2-cut) initiated PSP in 37 % of the rats and induced an apparent but small nocturnal PRL surge. The rats with POA-RS or F2-cut showed restoration of their regular estrous cyclicities. Cervical stimulation after POA-RS did not affect the initiation of nocturnal PRL surge induced by POA-RS alone. POA-RS after cervical stimulation also did not affect the initiation of nocturnal PRL surge induced by cervical stimulation, though a diurnal PRL surge was initiated in these rats. The cut made just before the diagonal band of Broca after cervical stimulation did not inhibit the occurrence of either surge. Nocturnal and diurnal PRL surges were manifested after cervical stimulation in the rats with chronic POA-RS or F2-cut and their vaginal cyclicities were resumed. These results suggest that the limbic forebrain structures are not indispensable for the initiation of nocturnal PRL surges induced by cervical stimulation but may modify the hypothalamic mechanism(s) initiating a nocturnal PRL surge through the rostral part of the hypothalamus.     

Behavioral and Morphological Studies of Fetal Neural Transplants into SCN-Lesioned Rats

We have studied the effects of fetal neuronal grafts on the temporal pattern of drinking behavior of suprachiasmatic nuclei (SCN)-lesioned adult rats. Additionally, in an independent set of animals, the immunohistochemical staining for vasopressin, vasoactive intestinal polypeptide, and neuropeptide Y and the retinal connections to the hypothalamus were studied. The behavioral experiments indicate that anterior hypothalamic transplants induced reorganization of the temporal pattern of drinking behavior when placed in the third ventricle of adult hosts bearing complete SCN lesions, but not when placed in a cavity in the occipital cortex. Such rhythmicity persists only when the animals were recorded under constant darkness but not under constant light, indicating that the restored rhythmicity was generated endogenously but that the oscillator was extremely sensitive to light. Fetal occipital cortex induced reorganization of the temporal pattern of previously arrhythmic hosts, but it disappeared when the animals were recorded under constant light or constant darkness. It is clear that this rhythmicity was exogenous. In contrast to the cortical transplants, the hypothalamic transplants showed a morphological organization similar to that found in the normal hypothalamus regardless of their placement in the host brain. From these observations it is concluded that development of neocortex is more affected by environmental factors than that of the hypothalamus. Both hypothalamic and cortical transplants induced sprouting of retinal fibers into the anterior hypothalamus and the grafted tissue. It is possible that such fibers could be the neuroanatomical substrate by which rhythmicity is induced by cortical tissue.     

Behavioral and Morphological Studies of Fetal Neural Transplants into SCN-Lesioned Rats

We have studied the effects of fetal neuronal grafts on the temporal pattern of drinking behavior of suprachiasmatic nuclei (SCN)-lesioned adult rats. Additionally, in an independent set of animals, the immunohistochemical staining for vasopressin, vasoactive intestinal polypeptide, and neuropeptide Y and the retinal connections to the hypothalamus were studied. The behavioral experiments indicate that anterior hypothalamic transplants induced reorganization of the temporal pattern of drinking behavior when placed in the third ventricle of adult hosts bearing complete SCN lesions, but not when placed in a cavity in the occipital cortex. Such rhythmicity persists only when the animals were recorded under constant darkness but not under constant light, indicating that the restored rhythmicity was generated endogenously but that the oscillator was extremely sensitive to light. Fetal occipital cortex induced reorganization of the temporal pattern of previously arrhythmic hosts, but it disappeared when the animals were recorded under constant light or constant darkness. It is clear that this rhythmicity was exogenous. In contrast to the cortical transplants, the hypothalamic transplants showed a morphological organization similar to that found in the normal hypothalamus regardless of their placement in the host brain. From these observations it is concluded that development of neocortex is more affected by environmental factors than that of the hypothalamus. Both hypothalamic and cortical transplants induced sprouting of retinal fibers into the anterior hypothalamus and the grafted tissue. It is possible that such fibers could be the neuroanatomical substrate by which rhythmicity is induced by cortical tissue.     

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.     

Hormonal regulation of maternal behavior in rats: stimulation following treatment with ectopic pituitary grafts plus progesterone

Changes in hormone secretions during pregnancy help to stimulate the onset of maternal behavior at parturition. To date, studies have demonstrated that estradiol (E2) appears to be a necessary component in the hormonal induction of maternal behavior in rats and other mammals. In the present study, we have reevaluated the contribution of E2, progesterone (P), and hormone-secreting pituitary grafts in the rapid induction of maternal behavior by measuring the behavioral effects of exposure to various combinations of P and prolactin-secreting ectopic pituitary grafts in the absence of estrogen. Adult hypophysectomized and nonhypophysectomized nulliparous rats were ovariectomized 2-3 days (Treatment Day 1) after their arrival in our laboratory. In Experiment #1, experimental, hypophysectomized rats were implanted s.c. with 6 P-filled Silastic capsules and given 2 anterior pituitary (AP) glands that were grafted beneath the kidney capsule on Treatment Day 1. Controls were given blank implants and were sham-grafted. P-filled and blank Silastic capsules were removed on Day 11, and behavioral testing was conducted once-a-day beginning on Day 12 for eleven days. Animals treated with P-plus-pituitary grafts displayed full maternal behavior significantly faster than did controls (median latencies of 3.0 and 7.5 days, respectively). In Experiment #2, nonhypophysectomized rats were assigned to one of three treatments. On Treatment Day 1, one group of rats received 6 P-filled Silastic implants and had 2 AP glands grafted under their renal capsules. A second group of animals received 6 P capsules and was sham-grafted, while controls were given blank implants and were sham-grafted.(ABSTRACT TRUNCATED AT 250 WORDS)     

Naltrexone partially inhibits the estrogen-induced increase in prolactin secretion and anterior pituitary weight

The effects of naltrexone, a specific opiate antagonist, on stimulation by estradiol benzoate (EB) of prolactin (PRL) release and anterior pituitary (AP) weight, were studied in gonadectomized female and male Sprague-Dawley rats. One week after castration, rats were injected for 10 days once daily with 2 μg EB alone, or together with twice daily injections of 2 mg naltrexone/kg body weight (BW). Blood was collected for radioimmunoassay of PRL by orbital sinus puncture on days 0 and 6, and by decapitation on day 11, at which time the AP was quickly removed, weighed and assayed for PRL.Serum PRL concentrations and AP weights were significantly increased by EB administration. These effects of EB were partially but significantly inhibited by naltrexone. These results suggest that endegenous opiates may be involved in the estrogen-induced rise in serum PRL and increase in pituatary weight.     

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.     

Induction of daily PRL surges in rats by chronic treatment with progesterone

The effect of a high plasma progesterone level on the PRL releasing mechanism was investigated in rats of both sexes. Progesterone levels were maintained by implanting silicone tubes filled with the steroid. In the intact female, 6 progesterone tubes (inner diameter 2 mm; outer diameter 3 mm; length 40 mm) were implanted subcutaneously on the estrous day. With 2- to 5- day latent periods, the daily rise in the plasma PRL level was observed coincident with the time of nocturnal surge in the pseudopregnant rats induced by cervical stimulation. The same treatment applied to ovariectomized rats induced by cervical stimulation. The same treatment applied to ovariectomized rats induced diurnal and nocturnal surges. The peak height was lower in ovariectomized rats than that in intact or normal pseudopregnant rats, and was restored to almost the normal range by concomitant implantation of estradiol with progesterone. This latter protocol, however, did not induce any PRL surge in chronically orchidectomized rats. These results suggest that chronically elevated progesterone levels can induce such PRL surges as are observed in pseudopregnant rats, estradiol enhances the magnitude of the PRL surge, and the progesterone sensitive central mechanism, controlling the PRL surge, does not exist in adult male rats.     

Relation of endogenous opioid peptides and morphine to neuroendocrine functions.

Morphine and the endogenous opioid peptides (EOP) exert similar effects on the neuroendocrine system. When adminstered acutely, they stimulate growth hormone (GH), prolactin (PRL), and adrenocorticotropin (ACTH) release, and inhibit release of luteinizing hormone (LH), follicle stimulating hormone (FSH),and thyrotropin (TSH). Recent studies indicate that the EOP probably have a physiological role in regulating pituitary hormone secretion. Thus injection of naloxone (opiate antagonist) alone in rats resulted in a rapid fall in serum concentrations of GH and PRL, and a rise in serum LH and FSH, suggesting that the EOP help maintain basal secretion of these hormones. Prior administration of naloxone or naltrexon inhibited stress-induced PRL release, and elevated serum LH in castrated male rats to greater than normal castrate levels. Studies on the mechanisms of action of the EOP and morphine on hormone secretion indicate that they have no direct effect on the pituitary, but act via the hypothalamus. There is no evidence that the EOP or morphine alter the action of the hypothalamic hypophysiotropic hormones on pituitary hormone secretion; they probably act via hypothalamic neurotransmitters to influence release of the hypothalamic hormones into the pituitary portal vessels. Preliminary observations indicate that they may increase serotonin and decrease dopamine metabolism in the hypothalamus, which could account for practically all of their effects on pituitary hormone secretion.     

Persistence of low hypothalamic dopaminergic activity after removal of chronic estrogen treatment

The purpose of this study was to determine whether inhibition of tuberoinfundibular dopaminergic (TIDA) neuron function which occurs during chronic estrogen administration persists after removal of the estrogen. Ovariectomized (OVX) Fischer 344 (F344) rats were implanted for 4 weeks with a Silastic capsule containing estradiol-17 beta (E2) and controls with an empty capsule for 4 weeks. Other rats which received E2 for 4 weeks had the capsule removed and experiments performed 4 weeks later. At the end of 4 weeks of E2 treatment, anterior pituitary (AP) weight was increased sixfold, serum prolactin (PRL) 65-fold, and AP DNA content fivefold over OVX control rats. Four weeks after removal of E2, AP weight, serum PRL, and AP DNA content declined, but remained significantly above OVX control values. At the end of 4 weeks of E2 treatment and after E2 withdrawal, release of [3H]dopamine (DA) from median eminence (ME) tissue superfused in vitro was lower than from ME of OVX control rats although [3H]DA accumulation was not significantly different among the treatment groups. Administration of apomorphine (APO), a dopamine agonist, significantly reduced plasma prolactin levels in OVX control rats, in rats at the end of 4 weeks E2 treatment, and in rats after 4 weeks of E2 withdrawal. Injection of haloperidol (HALO) produced similar increases in plasma PRL/estimated PRL-cell DNA in OVX controls, at the end of E2 treatment or after E2 withdrawal. However, injection of morphine (MOR), a drug which increases the release of PRL by inhibiting hypothalamic dopaminergic activity, resulted in a rise in plasma PRL/estimated PRL-cell DNA in OVX control rats that was significantly greater compared to rats at the end of E2 treatment or after E2 withdrawal. Since rats treated with E2 released less [3H]DA from ME tissue in vitro, and were less responsive to MOR, it can be that animals treated for 4 weeks with E2 show a decreased ability to release DA from TIDA neurons which persists even after termination of E2 treatment. These results suggest that chronic high circulating E2 levels result in a depression of TIDA neuronal activity which is sustained after E2 is removed.     

Further evidence for a hypothalamic site of action of atrial natriuretic factor: inhibition of prolactin secretion in the conscious rat

The presence of atrial natriuretic factor (ANF) in the hypothalamus and pituitary gland suggests a possible neuroendocrine action of the peptide. Because ANF has been shown to alter the activity of hypothalamic neurons and to interact with brain dopamine systems, we examined the possibility that it might be involved in the hypothalamic control of prolactin (PRL) and thyroid-stimulating hormone (TSH) secretion. Neither basal not stimulated release of PRL or TSH from cultured dispersed anterior pituitary cells was altered by doses of ANF ranging from 10(-11) to 10(-6) M. Similarly, the in vitro inhibition of PRL release by dopamine was not affected by the presence of ANF (10(-7) M). Plasma levels of PRL and TSH in conscious male rats infused for 30 min with 0.01 or 0.1 microgram ANF-kg-1.min-1 did not differ significantly from those present in saline infused controls. Third-cerebroventricular injection of saline (2 microL) or saline plus ANF (0.02, 0.1, 1.0, or 2.0 nmol) did not significantly alter TSH secretion; however, injection of the two highest doses of ANF resulted in significant inhibition of PRL release. Levels of PRL remained significantly reduced for 90 min after injection of 2 nmol ANF. The results indicate that ANF can act centrally to alter the release of neural factors responsible for the hypothalamic control of lactotroph function.     

Growth hormone is secreted by ectopic pituitary grafts and stimulates maternal behavior in rats

The onset of maternal behavior at parturition in rats is hormonally regulated. Recently, we reported that treatment of behaviorally inexperienced, hypophysectomized (hypox), ovariectomized (ovx) rats with a sequential steroid treatment of progesterone (P) and estradiol (E2), and either ectopic anterior pituitary grafts or prolactin (PRL), stimulated maternal responsiveness toward foster young. That growth hormone (GH) has a number of PRL-like activities led us to ask whether the actions of PRL on maternal behavior were specific to PRL or might be shared by other PRL-like protein hormone, i.e., GH. In Experiment 1 we quantified plasma concentrations of GH and PRL by RIA in groups of hypox female rats that were ovariectomized and treated with a combination of ectopic pituitary grafts (Days 1-23) and Silastic capsules filled with P (Days 1-11) and E2 (Days 11-23). Blood samples were collected from Days 1 to 23 of treatment. Both plasma PRL and GH levels increased after grafting, initially rising 10- to 60-fold by Day 4 and gradually declining throughout the remainder of the 23-day sampling period. Throughout the 3-week period after grafting plasma GH levels were as high or higher than those of PRL. In Experiment 2 the behavioral effects of exogenously administered ovine (o)-GH were measured in groups of hypox, ovx rats that were treated with P and E2 as in Experiment 1. Experimental rats were injected twice daily with 0.25 mg oGH beginning on Day 1. Testing for maternal behavior toward foster young was conducted daily from Day 12 to Day 22. In steroid-treated rats, GH treatment stimulated a more rapid onset of maternal behavior (latencies of 3 vs greater than 10 days for vehicle-injected controls). These data indicate that GH, like PRL, is secreted by ectopic pituitary grafts and is capable of stimulating maternal behavior.