Neurotensin-induced activation of hypothalamic dopaminergic neurons is accompanied by a decrease in pituitary secretion of prolactin and alpha-melanocyte-stimulating hormone.

The effects of neurotensin on the activity of hypothalamic tuberoinfundibular and periventricular-hypophysial dopaminergic (DA) neurons, and on the secretion of pituitary hormones that are tonically regulated by these neurons (i.e. prolactin and alpha-melanocyte-stimulating hormone [alpha MSH], respectively) were examined in estrogen-primed ovariectomized rats. The activity of tuberoinfundibular and periventricular-hypophysial DA neurons was estimated by measuring concentrations of the dopamine metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in the terminals of these neurons in the median eminence and intermediate lobe of the posterior pituitary, respectively. Intracerebroventricular administration of neurotensin caused a dose- and time-related increase in DOPAC concentrations in both the median eminence and intermediate lobe, and a concurrent decrease in plasma levels of prolactin and alpha MSH. These results suggest that neurotensin-induced inhibition of secretion of prolactin and alpha MSH from the pituitary may be due to the stimulatory action of this neuropeptide on the release of dopamine from tuberoinfundibular and periventricular-hypophysial neurons.     

Possible role of glutamate, aspartate, glutamine, GABA or taurine on cadmium toxicity on the hypothalamic pituitary axis activity in adult male rats

This work was designed to evaluate the possible changes in glutamate, aspartate, glutamine, GABA and taurine within various hypothalamic areas the striatum and prefrontal cortex after oral cadmium exposure in adult male rats, and if these changes are related to pituitary hormone secretion. The contents of glutamine, glutamate, aspartate, GABA and taurine in the median eminence, anterior, mediobasal and posterior hypothalamus, and in prefrontal cortex in adult male rats exposed to 272.7 mol l^–1 of cadmium chloride (CdCl₂) in the drinking water for one month. Cadmium diminished the content of glutamine, glutamate and aspartate in anterior hypothalamus as compared to the values found in the untreated group. Besides, there is a decrease in the content of glutamate, aspartate and taurine in the prefrontal cortex. The amino acids studied did not change in median eminence, mediobasal and posterior hypothalamus or the striatum by cadmium treatment. Plasma prolactin and LH levels decreased in rats exposed to the metal. These results suggest that (1) cadmium differentially affects amino acid content within the brain region studied and (2) the inhibitory effect of cadmium on prolactin and LH secretion may be partially explained by a decrease in the content of both glutamate and aspartate in anterior hypothalamus, but not through changes in GABA and taurine.     

The role of domperidone in the regulation of prolactin release in rats

Effects of domperidone, a dopamine antagonist, on prolactin release in female rats were studied. Oral administration of domperidone for 14 days caused a significant increase in serum prolactin levels in mature female rats. The routes by which domperidone exerted its effects on prolactin release were studied by a in vitro incubation system using rat pituitary tissues. Pituitary halves were incubated with (1) domperidone, (2) dopamine, (3) dopamine plus domperidone, (4) hypothalamic extracts from rats which had been treated with control meal (control hypothalamic extract), (5) control hypothalamic extract plus domperidone, and with (6) hypothalamic extract from rats which had been treated with domperidone for 14 days (domperidone-treated hypothalamic extract). Pituitary halves, when incubated alone, released a significant amount of prolactin into the incubation medium after 24 hours incubation, which was completely inhibited by dopamine or control hypothalamic extract. The addition of domperidone could not reverse the inhibitory effect of dopamine or control hypothalamic extract. On the other hand, domperidone-treated hypothalamic extract showed no inhibitory effects on prolactin release. These results indicated that domperidone could increase serum prolactin levels in female rats by acting primarily at the hypothalamus.     

Long-term ACTH induced diminished responsiveness of prolactin secretion to morphine

The effect of morphine on plasma prolactin level and on dopamine turnover in the median eminence was studied using adult male rats chronically treated with ACTH. It was found that the ACTH pretreatment caused a decrease in the effect of morphine on prolactin secretion and prevented the inhibitory effect of morphine on dopamine turnover measured in the median eminence. The prolonged ACTH administration did not influence the prolactin content of the pituitaries and the in vitro dopamine sensitivity of lactotroph cells. Acute dexamethasone injection did not change the morphine-caused prolactin release. These results suggest that chronic ACTH treatment (possibly via corticosterone hyperproduction) elicits an opiate-tolerance like state of tuberoinfundibular dopaminergic neurons.     

Co-transport of sex hormone-binding globulin/SHBG with oxytocin in transport vesicles of the hypothalamo-hypophyseal system.

The intrinsic expression of sex hormone binding globulin (SHBG) in magnocellular hypothalamic neurons, in part co-localized with either vasopressin or oxytocin, was recently described. This study is focused on the ultrastructural localization of SHBG in the hypothalamo-neurohypophyseal pathway in rats. Immunostaining for SHBG in the hypothalamic perikarya was increased by colchicine treatment, indicating that the steroid-binding globulin is subject to rapid axoplasmic transport along with the classical posterior lobe peptides. With immunoelectron-microscopic double labeling, we found co-localization of oxytocin and sex hormone binding globulin in a portion of the large dense-core vesicles in paraventricular and supraoptic perikarya and in axonal varicosities in the median eminence and in the posterior lobe. Our observations show that SHBG is processed, transported and stored along with oxytocin suggesting that SHBG is released from nerve terminals in the posterior lobe, the median eminence and possibly the brain similarly to and in conjunction with oxytocin.     

Neuroendocrinology of Teleosts

The nucleus preopticus has been shown to receive afferent inputfrom certain cranial nerves and the spinal cord. In addition,the nucleus preopticus and its tracts can synthesize and transporthormones about as rapidly as a mammal can. The nucleus preopticusis functionally involved in the spawning reflex behavior. The hypothalamic control of each of the adenohypophysial hormonesis discussed. There is conflicting and incomplete evidence forthe control of melanocyte-stimulating hormone (MSH), prolactin,and somatotropin. Secretion of prolactin and MSH may each becontrolled by an inhibitory factor. Corticotropin secretionhas been shown to be controlled by corticotropin releasing factor(CRF). There is a negative fedback effect by cortisol on thepituitary to suppress corticotropin secretion. Gonadotropinsecretion is controlled by gonadotropin releasing factor (GRF).A part of the nucleus lateralis tuberis is involved in the controlof gonadotropin secretion. A great deal of indirect evidenceindicates that a thyrotropin inhibitory factor (TIF) controlsthyrotropin secretion. There is a negative feedback effect bythyroxine on the pituitary to suppress thyrotropin secretionand a positive feedback effect on the hypothalamus to stimulateTIF secretion. The above findings are restricted to only one or two speciesin each instance. It is not known how general the above mechanismsof control are found throughout the teleosts.     

Effect of nitric oxide on prolactin secretion and hypothalamic biogenic amine contents

Involvement of nitric oxide (NO) in the episodic secretion of prolactin was studied in conscious freely moving adult rats. Prolactin secretion was pulsatile in all animals of either group during the bleeding period (from 10:30 h to 13:30 h). Administration of N(omega)-nitro-L-arginine methyl ester (L-NAME), a NO synthase inhibitor, increased mean plasma levels of prolactin, and the absolute amplitude of prolactin peaks during the whole bleeding period as compared to values found in the control group. L-NAME increased norepinephrine (170%), dopamine (58.27%) and serotonin contents (30%) in the anterior hypothalamus. In the median eminence, dopamine and serotonin contents decreased (19.79% and 33.9% respectively) after L-NAME as compared to the values found in controls. In addition, norepinephrine content increased in mediobasal hypothalamus (79.6%) of rats treated with L-NAME. The results indicate that changes in NO production may modify the episodic secretion of prolactin. These effects were associated with changes in hypothalamic and median eminence biogenic amines.     

Twenty-four hour rhythm of plasma prolactin in female rabbit pups. Correlation with hypothalamic and adenohypophysial dopamine, serotonin, gamma-aminobutyric acid and taurine content

Lactation in the rabbit is a nocturnal activity, extremely short and regular, that can be a strong synchronizer for the development of circadian rhythmicity in the pups. In the present study, 24-h rhythmicity of plasma prolactin and median eminence and anterior pituitary content of dopamine (DA), serotonin (5HT), gamma-aminobutyric acid (GABA) and taurine were examined in 11 days old female pups kept under 16 h light:8 h dark photoperiods (lights on at 08:00 h). Groups of six to seven female rabbit pups were killed by decapitation at six different time points throughout a 24-h cycle, starting at 09:00 h. Plasma prolactin levels changed significantly throughout the day, showing two peaks, one at first half of rest span (at 13:00 h) and another one at the beginning of the scotophase (at 01:00 h), just preceding doe visit. Median eminence DA content changed in a bimodal way as a function of time of day, displaying two maxima, at the beginning of the rest span and of the activity phase. Median eminence DA and plasma prolactin correlated significantly in an inverse way. Two maxima in median eminence 5HT levels were found, about 4 h in advance to the prolactin peaks. Circulating prolactin correlated inversely with median eminence 5HT content and directly with adenohypophysial 5HT content. Median eminence GABA content reached its maximum at the beginning of the scotophase and correlated significantly with plasma prolactin concentration. A positive correlation between plasma prolactin and adenohypophysial taurine content was observed. These results show that the circadian rhythmicity in prolactin secretory mechanisms in female rabbit pups develops during the early neonatal life.     

Involvement of the hypothalamus in opiate-stimulated prolactin secretion

Administration of opiate agonists to rats is known to elevate plasma prolactin, an effect which is antagonised by the opiate antagonist naloxone. However, this appears not to be a result of a direct action at the pituitary gland. We report here that opiate agonists stimulate prolactin secretion from isolated adenohypophysial cells when they are coincubated with hypothalamic fragments. Both morphine and Met-enkephalin stimulated prolactin secretion by 1.84 fold and 1.50 fold respectively, and this was antagonised by naloxone. These findings support the hypothesis that one site of action of opioid compounds on pituitary hormone secretion is at the level of hypothalamus.     

Aminergic regulation of neuroendocrinological functions: theoretical background and some clinical examples

Remarkable progress has been made during recent years in the central regulation of the hypothalamic releasing and inhibiting factors and the respective anterior pituitary hormones. There are two nearly universal inhibitory organizations: short tuberoinfundibular dopamine (TIDA) neurons and somatostatinergic system originating from the periventricular hypothalamus and terminating to the median eminence. It is now known that e.g. dopamine, noradrenaline and acetylcholine enhance while 5-hydroxytryptamine and GABA inhibit somatostatin secretion. These transmitters are also involved in the regulation of all releasing factors and pituitary hormones. Clinical applications have been developed based on the regulation of prolactin and growth hormone. Inhibitory TIDA neurons are undoubtedly the major determinants of prolactin secretion. Hyperprolactinaemia is one of the most common endocrinological side-effects of the drugs antagonizing dopaminergic transmission. Expectedly, dopaminergic drugs (bromocryptine, lergotrile, piribedil, dopamine and levodopa) are quite effective in reducing high prolactin levels regardless of the reason. The secretion of growth hormone is predominantly under dual dopaminergic control: hypothalamic stimulation and pituitary inhibition. The former masters the function of the normal gland, while the peripheral inhibitory component takes over in acromegalic gland. Hence dopaminergic drugs are able to reduce elevated growth hormone levels in 30-50% of the acromegalic patients. In normal man, dopamine agonists increase growth hormone levels. An analogous situation can be seen in Cushing's disease regarding ACTH secretion.     

Effects of passive immunization against oestradiol-17 beta on some endocrine values of the male lamb

Passive immunization of male lambs against oestradiol-17 beta from 2 to 16 weeks of age significantly elevated androgen concentrations in plasma and depressed the median eminence content of dopamine. Removal of endogenous oestrogens had no significant effects on plasma FSH, LH or prolactin concentrations or on testicular growth and hypothalamic content of GnRH. These results suggest that endogenous oestrogens may indirectly suppress testicular androgen secretion by exerting a stimulatory influence on hypothalamic dopaminergic neurones, which in turn may inhibit GnRH secretion by the median eminence.     

Corticotropin releasing factor (CRF)-like immunoreactivity in the hypothalamus and posterior pituitary of the goat, bovine, rat, monkey and human

Goat hypothalamic extract prepared by HCl extraction and chromatographed on a Sephadex G-50 column showed two immunoreactive CRF peaks. Most of the immunoreactivity coeluted with synthetic ovine CRF, and a small peak eluted near the void volume. Bovine, monkey, rat and human hypothalamic extracts prepared by acid-acetone or acid-methanol extraction showed three immunoreactive peaks. Most of the immunoreactivity coeluted with ovine CRF, and other smaller peaks eluted near the void volume and slightly before arginine vasopressin. Goat hypothalamic extract showed the highest cross-reactivity with anti-ovine CRF serum, followed by bovine hypothalamic extract. Less cross-reactivity was found in human, rat and monkey hypothalamic extracts. CRF immunoreactivity in goat hypothalamic extract coeluted with ovine CRF on reversed phase high performance liquid chromatography (HPLC) and main CRF immunoreactivity in human and rat hypothalamic extracts eluted slightly later than ovine CRF. These results suggest that there is a heterogeneity among the CRF molecules in these species and that goat CRF may be more similar to that of sheep CRF and the amino acid sequence or molecular weight of other animals CRF may be different from that of sheep CRF. The monkey posterior pituitary and rat neurointermediate lobe showed similar elution patterns of CRF immunoreactivity to their hypothalamic extracts on Sephadex gel filtration and HPLC. These results indicate that the posterior pituitary contains a similar CRF to hypothalamic CRF.     

Temporal sequence of neuroendocrine events associated with the transfer of male golden hamsters from a stimulatory to a nonstimulatory photoperiod

The transfer of male golden hamsters from long day (LD) to short day (SD) conditions results in gonadal atrophy within 8 weeks and significant reductions in LH, FSH, and prolactin (Prl) secretion as early as 4 weeks. Changes in hypothalamic neurotransmitter metabolism precede these changes in pituitary hormone secretion. Thus median eminence norepinephrine (NE) turnover declines steadily after SD exposure, although the differences as compared to turnover in LD hamsters are not significant until Week 4. Median eminence dopamine (DA) turnover is reduced significantly within 1 week. Turnover of NE and DA in the medial basal hypothalamus also changes significantly within 1 or 2 weeks of SD exposure, but the changes are not maintained through Week 8, despite continued reductions in levels of circulating LH, FSH, and Prl. Reductions in median eminence NE metabolism appear to be responsible for the decrease in LH and FSH release. Initial decreases in Prl release appear to be hypothalamic in origin, but the hypothalamic factor(s) responsible for this change is not evident. An increase in inhibitory input from tuberoinfundibular dopaminergic neurons is clearly not involved.     

Effect of chronic hyperprolactinemia on daily changes of glutamate and aspartate concentrations in the median eminence and different hypothalamic areas of male rats

The 24h changes of glutamate (GLU) and aspartate (ASP) were studied in the median eminence (ME) and hypothalamic areas. It was analyzed whether prolactin may change their daily patterns. The hypothalamic concentration of these amino acids was measured by high-performance liquid chromatography (HPLC) with fluorometric detection. Plasma prolactin levels increased over the 24h light-dark cycle after pituitary grafting compared to controls, and its circadian rhythm was disrupted. In controls, aspartate and glutamate in the hypothalamic areas studied followed a specific daily variation or showed no rhythmicity. In the median eminence, hyperprolactinemia seem to phase advance the aspartate or glutamate peaks from 16:00 to 12:00. In the mediobasal hypothalamus, hyperprolactinemia altered daily changes of aspartate and significantly decreased its concentration. Also, it seems to delay the nocturnal glutamate peak compared to controls. In the posterior hypothalamus, hyperprolactinemia did not change aspartate and glutamate concentrations and their daily changes, although it increased the glutamine concentration. These data show the existence of 24h changes of amino acid concentration in three of the hypothalamic regions studied. Increased plasma prolactin levels differentially affected these patterns depending on the hypothalamic area analyzed. (Chronobiology International, 17(5), 631-643, 2000)     

Hypothalamic and hormonal control of the photoperiodically induced vernal functions in the White-crowned Sparrow,Zonotrichia leucophrys gambelii

To assess the role of the hypothalamo-hypophysial complex in the control of photoperiodically induced vernal premigratory responses in the White-crowned Sparrow, the effects of hypothalamic lesions and systemic administration of several hormones on these responses were investigated. Lesions that destroyed the posterior median eminence (PME) or the entire median eminence (ME) inhibited photoperiodically induced testicular growth, premigratory fattening and Zugunruhe. Lesions in the basal infundibular nucleus (IN) that resulted in complete inhibition of testicular growth abolished Zugunruhe, but allowed varying degrees of fattening. The systemic administration of prolactin, testosterone propionate (TP) or the combination thereof in the PME-lesioned birds induced fattening similar to that observed in photostimulated controls but did not induce Zugunruhe. It is concluded that testosterone and prolactin are the most important hormones involved in the control of vernal premigratory fattening. The role of these hormones in the induction of vernal Zugunruhe is not positively proven.     

beta-(-4 Chlorophenyl) GABA (baclofen) inhibits prolactin and thyrotropin release by acting on the rat brain

Baclofen, a GABA B agonist, inhibits prolactin release due to different kinds of stress. In the present study its effect was evaluated in several endocrine experimental situations to explore the specificity of this effect, as well as the site of action of the drug. Baclofen significantly inhibited prolactin and thyrotropin outputs induced by 25 min of suckling, without altering milk ejection or LH secretion. The effect was also tested in median eminence-lesioned rats and in in vitro incubations. Baclofen did not modify prolactin levels in rats in which brain control of the pituitary secretion was eliminated by destruction of the median eminence, and it did not inhibit prolactin or thyrotropin secretion from incubated hemipituitaries. It is postulated that baclofen inhibits prolactin and thyrotropin secretion by acting on GABA B receptors related to the brain control of pituitary secretion.     

Tanycyte absorption affected by the hypothalamic deafferentation in Japanese quail,Coturnix coturnix japonica

In Japanese quail, Coturnix coturnix japonica the tanycytes of the median eminence absorbed peroxidase injected into the third ventricle. The number of tanycytes showing peroxidase reaction was greater in the posterior median eminence than in the anterior median eminence. Following hypothalamic deafferentation, the tanycyte absorption was augmented both in the posterior and anterior median eminence. These findings suggest that axons of some neurons, which have inhibitory action on the tanycyte absorption, were transected by deafferentation resulting in augmentation of tanycyte absorption. A considerable number of ependymal cells lining the upper portion of the third ventricle and those of the pars nervosa also absorbed peroxidase. In birds with a deafferented hypothalamus, photostimulated ovarian growth was completely inhibited.     

EFFECT OF CHRONIC HYPERPROLACTINEMIA ON DAILY CHANGES OF GLUTAMATE AND ASPARTATE CONCENTRATIONS IN THE MEDIAN EMINENCE AND DIFFERENT HYPOTHALAMIC AREAS OF MALE RATS

The 24h changes of glutamate (GLU) and aspartate (ASP) werestudied in the median eminence (ME) and hypothalamic areas. It was analyzedwhether prolactin may change their daily patterns. The hypothalamic concentrationof these amino acids was measured by high-performance liquid chromatography(HPLC) with fluorometric detection. Plasma prolactin levels increased overthe 24h light-dark cycle after pituitary grafting compared to controls, andits circadian rhythm was disrupted. In controls, aspartate and glutamate inthe hypothalamic areas studied followed a specific daily variation or showedno rhythmicity. In the median eminence, hyperprolactinemia seem to phase advancethe aspartate or glutamate peaks from 16:00 to 12:00. In the mediobasal hypothalamus,hyperprolactinemia altered daily changes of aspartate and significantly decreasedits concentration. Also, it seems to delay the nocturnal glutamate peak comparedto controls. In the posterior hypothalamus, hyperprolactinemia did not changeaspartate and glutamate concentrations and their daily changes, although itincreased the glutamine concentration. These data show the existence of 24hchanges of amino acid concentration in three of the hypothalamic regions studied.Increased plasma prolactin levels differentially affected these patterns dependingon the hypothalamic area analyzed. (ChronobiologyInternational, 17(5), 631–643, 2000)     

On the relations between the hypothalamus and the anterior pituitary in Rana temporaria

Summary Dawson (1952) showed that, in Rana, many nerve terminals end round the capillaries of the venous portal system of the median eminence. Our observations not only confirm these facts but show as well that, besides the posterior lobe, the outer zone of the median eminence is also a centre of accumulation of neurosecretory material derived from the pre-optic nucleus. The amount of this neurosecretory material is moreover subject to a certain variation in connection with the seasons and with experimental conditions. The idea is put forward that the outer zone of the median eminence of Rana has to be considered as an analogical organ of the posterior lobe. Indeed, in the median eminence, the same morphological facts can be found, which are advanced for the conception that the posterior lobe is a centre of accumulation and a place of release of neurosecretory material originating from the pre-optic nucleus. On the basis of our observations we presume that the hypothalamo-hypophyseal neurosecretory system of Rana can be divided in two sub-units. System I ends in the posterior lobe; system II in the outer zone of the median eminence. The data of the literature indicate that the two systems also probably exist in the higher vertebrates. From these facts it is obvious that the neurosecretory material is transported from the pre-optic nucleus, via the tract, towards the outer zone of the median eminence.     

Interaction between opiates and hypothalamic dopamine on prolactin release.

Opiate stimulation of prolactin (PRL) release appears to involve a hypothalamic mechanism(s). The present study utilized both central acting drugs and direct measurement of hypothalamic dopamine (DA) to investigate this problem. Administration of L-dopa, the precursor of DA; piribedil, a DA agonist; or amineptine, a DA reuptake inhibitor, each decreased serum PRL concentrations. Morphine sulfate (MS) and haloperidol (HAL) significantly increased serum PRL levels. L-dopa and piribedil reversed the stimulatory effect of MS on serum PRL concentrations by increasing dopamine activity. MS blocked the inhibitory effects of amineptine on serum PRL release, possibly by decreasing the concentration of DA available for reuptake. Injection of subeffective doses of HAL concurrently with a subeffective dose of MS increased serum PRL concentrations, by an additive inhibitory action on dopaminergic activity. β-endorphin, an endogenous opioid peptide, decreased the rate of DA turnover in the median eminence, and increased serum PRL levels approximately 10 - fold. These observations indicate that opiates stimulate PRL release by decreasing DA activity in the median eminence.