Interactions of Dopamine and Thyrotropin-Releasing Hormone in the Regulation of Prolactin Release in Lactating Rats*
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Dopamine, secreted by the median eminence into hypophysial stalk blood, accounts for much of the inhibition of PRL release known to be exerted by the hypothalamus, and recent studies of lactating rats have revealed a brief decrease (60–70% for 3–5 min) in hypophysial stalk plasma dopamine concentrations immediately after the onset of a simulated suckling stimulus (electrical stimulation of a mammary nerve trunk). In the present study, we investigated the regulatory significance of this decrease for the increased PRL secretion evoked by this stimulus and, in addition, researched the effect of TRH on plasma PRL levels when it was administered before and after the decrease in dopamine. Control lactating rats anesthetized with urethane exhibited low and unvarying levels of plasma PRL (mean ± SEM 3.5 ± 0.6 ng/ml). Intraperitoneal injection of αmethyl- p-tyrosine (AMPT) resulted in a 120-fold elevation of plasma PRL levels. Dopamine infusions (1.0 μg-min/kg BW) into AMPT-treated rats, achieving stalk plasma dopamine concentrations in the range normally found there (8.4 ± 1.6 ng/ml), suppressed plasma PRL levels by 67%. However, a brief decrease (70% for 5 min) in the dopamine infusion rate to mimic the pattern of dopamine secretion in hypophysial stalk blood after a simulated suckling stimulus did not alter plasma PRL concentrations. TRH injection (300 ng/kg BW, iv) failed to acutely increase plasma PRL levels in control rats with low basal levels of plasma PRL, in AMPT-treated rats with high basal PRL levels, or in AMPT-treated dopamine-infused rats exhibiting intermediate plasma PRL levels; however, it did so in rats undergoing a 5-min 70% decrease in the rate of dopamine infusion. The magnitude of the increase was about 3-fold and lasted for 20–30 min. These results suggest that the brief decrease in dopamine secretion evoked by suckling does not, by itself, increase PRL secretion. However, it may condition the pituitary to respond to a putative PRL-releasing factor (TRH). Thus, these results suggest that the increased PRL secretion after suckling is due to a decrease in the secretion of dopamine and an increase in the secretion of a PRL-releasing factor.Keywords:
Median eminence
Pituitary stalk
Basal (medicine)
Median eminence
Pituitary stalk
Medial forebrain bundle
Posterior pituitary
Diencephalon
Preoptic area
Vesicular monoamine transporter
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Recent evidence indicates that thyroid hormones can regulate thyrotropin secretion in vivo in part by inhibiting thyrotropin-releasing hormone (TRH) secretion itself. Therefore, to explore whether triiodothyronine (T3) interacts with the specific hypothalamic area involved in thyrotropin (TSH) secretory regulation, the paraventricular nucleus (PVN), Palkovitz micropunches from eight nuclear regions were obtained from 1,000-µm frozen coronal brain slices for immunoassay determinations of TRH. Rats were treated either with parenteral L-T3 for 6 days to induce experimental thyrotoxicosis, or 0.15 M saline. The induction of thyrotoxicosis was confirmed by demonstrating that mean plasma TSH concentrations fell from 108 to < 10 µU/ml (p < 0.01). TRH concentrations in the PVN were reduced concomitantly after L-T3 from 1.9 to 1.1 ng/mg protein (p < 0.05). No reductions in TRH concentrations during T3 treatment occurred in other nuclear groupings except in the posterior hypothalamic nucleus. Total TRH content in the median eminence declined also in T3-treated animals from 1.77 to 1.29 ng, representing a 32% reduction (p < 0.01). No signifcant change was seen in the median eminence content of the TRH structurally related dipeptide, cyclo(His-Pro). The data herein indicate that experimental thyrotoxicosis in the rat is associated with a selective reduction in TRH concentrations in the PVN, documenting T3 effects upon hypothalamic TRH metabolism per se.
Median eminence
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The acute effect of selective surgical interruption of the anterior pituitary’s blood supply on the release of ACTH has been investigated in surgically stressed rats. The corticosterone secretory rate was used to evaluate the release of ACTH. In intact, sham-operated animals, corticosterone secretion was near maximal throughout a 50-min observation period. Removal of the pituitary greatly suppressed the secretion of corticosterone. Posterior lobectomy or transection of the portal vessels in the upper stalk had no apparent effect on ACTH release. This finding was interpreted to mean that the posterior pituitary and post-chiasmatic eminence are not obligatory sources of CRF. Transection of the pituitary stalk greatly suppressed ACTH release. This finding supports the view that the caudal hypophysial arteries do not provide the anterior pituitary with a significant amount of blood via the short portal vessels. Transection of the peduncular arteries or the stalk portal vessels in the lower stalk suppressed ACTH release. This finding is consistent with the notion that CRF enters portal blood via the post-peduncular and/or pituitary stalk capillaries. These findings indicate that CRF comes from the stalk, postpedunuclar eminence and/or the cerebrospinal fluid. (Endocrinology86: 590, 1970)
Median eminence
Pituitary stalk
Corticosterone
Posterior pituitary
Blood supply
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The size of the neuro-vascular contact surface was estimated along the median eminence (ME) and proximal pituitary stalk (PS) of adult rats using serially cut 1 μm thick plastic sections. It was found 26% larger in female than in male animals. The dorsal surface of the pars tuberalis was used as reference surface, and its size was estimated in the same way. The average rate of increase of the contact surface with respect to the reference surface was 3.05 and 2.98 in females and 2.34 and 2.35 in males. The reference surface was divided into small components and also the regional distribution of the rate of increase of the contact surface was analyzed. Very folded contact surface areas were found scattered in the rostral half of the ME. Folded areas made up the ME on both sides of the midline and the dorsal and ventral surfaces of the PS, whereas relatively smooth areas are localized along the 2 margins of the ME and the 2 sides of the PS. The results were correlated with the known termination sites of dopamine and various hypothalamic hormone containing pathways.
Median eminence
Pituitary stalk
Pars tuberalis
Stalk
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The concentration of dopamine, norepinephrine, epinephrine and serotonin was determined in 6 rostrocaudal segments of the median eminence, 2 segments in the pituitary stalk, in the retrochiasmatic area and the pituitary lobes by radioenzymatic microassay in adult rats. The level of dopamine and norepinephrine was measured separately in the medial and lateral portions of the median eminence. All four amines measured were found unevenly distributed inside the median eminence: 1. the highest dopamine level was detected in the middle-caudal portions of the median eminence and in the rostral parts of the pituitary stalk; 2. high norepinephrine concentration was found in the retrochiasmatic area and this gradually diminished caudalwards; 3. relatively high epinephrine level was present in the rostral median eminence and retrochiasmatic area, but that in the caudal median eminence and pituitary stalk was low; 4. the level of serotonin increased caudalwards and showed a highest value in the caudal portion of the pituitary stalk. Relatively high dopamine and serotonin levels were also detectable in all three pituitary lobes where the concentration of norepinephrine was low and that of epinephrine was undetectable.
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Pituitary stalk
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IT HAS BEEN ESTABLISHED that severing the hypophysial stalk in monkeys, without injury to the median eminence of the tuber cinereum, causes no evident modification in the water intake or urine output (i, 2, 3). But if the resection is so high that only half or less of the median eminence is left intact, severe diabetes insipidus invariably follows, as is also the case when the supraopticc hypophysial nerve tract is cut bilaterally in the hypothalamus (4). Since there are species differences, it is not only desirablebut in many cases necessary to check animal experiments by comparable clinical cases before application can be made to man, although there are indications that about the same results should be expected in human beings in this instance (5, 6). The present case is also of special interest because elevated blood pressure in certain cases has been regarded by some as an expression of hyperactivity of the hypophysis.
Median eminence
Pituitary stalk
Infundibulum
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The hypophysial stalk and the median eminence were cauterized electrically in rats 20–24 h after birth, and the growth and histogenesis and functional capacities of the endocrine glands of these rats were examined 20–23, 40–43, and 60–70 days after the operation. The arcuate nuclei showed degenerative alterations in rats with lesions of the median eminence. The supraoptic and paraventricular nuclei showed degenerative changes in rats with an isolated pituitary stalk. In all these animals, the growth and development of the gonads were greatly reduced, and the functional activities of the thyroid and adrenal glands were also affected. The results indicated that normal growth and development of endocrine organs may require intact vascular and afferent neuronal coordinations between the hypothalamus and the hypophysis for the transportation of factors releasing hypophysial trophic hormones.
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Pituitary stalk
Endocrine gland
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To identify the specific thyrotropin-releasing hormone (TRH)-containing neurons projecting to the median eminence (ME), a retrograde tracing method with horseradish peroxidase (HRP) was combined with immunocytochemical staining for TRH. Three days after HRP injection restricted to the ME, several TRH-positive neuronal perikarya were found to contain HRP. Such double-stained cells were exclusively distributed in the anterior parts of the periventricular nucleus and the most medial parts of the paraventricular nucleus. Few double-stained cells were observed in other parts of the brain examined. The present observations appear to demonstrate that the specific TRH neurons projecting to the ME are located along the border of the third ventricle, anterior to the ME.
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Tea normal volunteers received 100 to 800 ug of TRH intravenously. Serum prolactin was measured by a specific radioimmunoassay before and at intervals after TRH administration. Serum prolactin began to rise within 5 minutes and was maximal after 15 to 20 minutes. The mean peak response at 15 minutes was 11 times the fasting level. Serum prolactin had returned to the baseline by 180 minutes. It is concluded that TRH may be closely related to prolactin releasing factors in crude hypothalamic extracts.
Serum concentration
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