Showing papers on "Hypothalamus published in 1977"

Gonadotrophin-releasing hormone deficiency in a mutant mouse with hypogonadism

Abstract: FAMILIAL hypogonadism in man, due to an isolated deficiency of gonadotrophin secretion, has been well documented1–6, but difficult to investigate because of the lack of a suitable animal model4. We report here the genetic and endocrinological background of a mutant strain of mouse in which the testes and ovaries fail to develop postnatally. The primary cause of this seems to be a deficiency in hypothalamic gonadotrophin-releasing hormone (GnRH) with a consequent reduction in pituitary content and circulating levels of luteinising hormone (LH) and follicle-stimulating hormone (FSH). By analogy with the Brattleboro rat (genetic defect in vasopressin synthesis) this mutant should prove useful for studying the synthesis of hypothalamic releasing hormones as well as the role of the hypothalamic–gonadotrophin system in sexual differentiation, puberty, folliculogenesis and spermatogenesis. The mutant has been named hypogonadal, symbol hpg.

Regulatory peptides of the hypothalamus.

Abstract: The peptides that are the principal subject of this review were originally detected in extracts of the hypothalamus as a result of their effects on the secretory functions of the anterior pituitary gland. According to the portal-vessel chemotransmitter hypothesis ( 155, 192), neurosecretory cells in the hypothalamus produce factors or hormones which reach the adenohypophysis by way of the hypothalamic-hypo­ physeal portal system. These neural factors act in concert with other blood-borne signals from the periphery to regulate the functions of the various anterior pituitary cells. To date, three peptides have been purified and characterized, and furthermore shown to have unequivocal hypophysiotropic activities by numerous investigators. These are TRF, LRF, and somatostatin (SS) whose alternative names, sequences, and principal actions on the anterior pituitary are shown in Table 1 . All three of these peptides have biological actions on the central nervous system (CNS) in addition to their effects on the anterior pituitary. Furthermore, TRF, LRF, and somatostatin are widely distributed throughout the brain, and somatostatin is found in and can influence the function of the pancreas and gastrointestinal tract as well. In general, the hypothalamic regulatory peptides (HRP) appear to act as local extracellular signals or messengers, as cells containing (producing) the HRP are found in, are adjacent to, or have restrictive vascular or possibly cerebral spinal-fluid links to cells that can respond to these peptides. Peptides with such local actions have been termed members of the paracrine rather than the endocrine system ( 152). The observations indicating that these peptides are exclusively neither hypo­ thalamic nor hypophysiotropic present problems of classification as well as nomen­ clature to neuroendocrinologists. In the interest of historical continuity, we continue to refer to these peptides as hypothalamic and maintain the original "releasing­ factor" terminology until such time as IUPAC-IUB-approved trivial names gain acceptance. Analyses for the purpose of categorizing the HRP as hormones, neurotransmitters, or a separate class of extracellular messengers reveal the

Hypothalamic changes during the immune response.

Abstract: The immune system is subject to an array of identified autoregulatory processes, but immunoregulation may also have a further basis in a network of immune-neuroendocrine interactions. Two antigens each produced an increase of more than 100% in electrical activity of individual neurones in the ventromedial but not in the anterior nucleus of the rat hypothalamus. Animals that failed to respond to antigen manifested no increase in the firing rate. These findings constitute the first evidence for a flow of information from the activated immune system to the hypothalamus, suggesting that the brain is involved in the immune response.

Hypothalamic-pituitary vasculature: evidence for retrograde blood flow in the pituitary stalk.

Abstract: Retrograde transport of pituitary hormones in the pituitary stalk vasculature was investigated in anesthetized male rats in which the pituitary gland was intact and in animals in which the anterior pituitary, posterior pituitary, or entire pituitary gland had been removed 30 to 60 min before use. Blood was collected for 1.5 to 2 h by free flow from a single long portal vessel through a microcannula, the tip of which was pointed toward the hypothalamus. An arterial blood sample was obtained at the end of each collection of portal blood. The concentrations (ng\ml) of LH, TSH, prolactin, ACTH, α-MSH, and vasopressin, determined by radioimmunoassay, in portal plasma from rats with intact pituitary glands were as follows: LH, 2,320 ± 874 (mean and SE); TSH, 10,180 ± 1,471; prolactin, 4,858 ± 884; ACTH, 82 ± 17.0; a-MSH, 103 ± 17.8; vasopressin, 2.4 ± 1.0. The concentrations of these hormones in arterial plasma of these rats were as follows: LH, <20; TSH, 149 ± 22; prolactin, 25 ± 5.0; ACTH, 0.36 ± 0.05; α-MSH,...

The origin of the vasopressinergic and oxytocinergic fibres of the external region of the median eminence of the rat hypophysis.

Abstract: The origin of the vasopressinergic and oxytocinergic nerve fibres of the external region of the rat median eminence was investigated by means of hypothalamic lesions, adrenalectomy and immunocytochemistry. The results obtained in bilaterally adrenalectomized animals with complete, or incomplete, destruction of the suprachiasmatic nuclei showed that, at least, the great majority of the vasopressinergic and oxytocinergic nerve fibres of the external region of the rat median eminence do not originate from the suprachiasmatic nuclei. From the observations obtained in bilaterally adrenalectomized animals with total or subtotal destruction of both paraventricular hypothalamic nuclei, it appears that the paraventricular nuclei must be the origin of (nearly) all the vasopressinergic and oxytocinergic nerve fibres of the external region of the rat median eminence. The results strongly suggest that both types of fibres originate from all parts of the paraventricular nuclei.

beta-Lipotropin: localization of cells and axons in rat brain by immunocytochemistry.

Abstract: Using specific antisera to human beta-lipotropin, we have visualized cells and axons with beta-lipotropin-like immunoreactivity in rat brain and pituitary. The beta-lipotropin so localized is well delineated and contained in the cytoplasm of cells and in beaded axons. Areas of greatest beta-lipotropin content are hypothalamus (with cell bodies in the medial basal hypothalamus and arcuate regions), periventricular nucleus of the thalamus, ansa lenticularis, zona compacta of the substantia nigra, medial amygdaloid nucleus, zona incerta, periaqueductal central gray area, locus ceruleus, and a few fibers in the reticular formation. The question of the exact relationship of beta-lipotropin and methionine-enkephalin remains open, because some brain areas contain both substances and some areas contain only one or the other.

Aromatization and 5α-Reduction of Androgens in Discrete Hypothalamic and Limbic Regions of the Male and Female Rat1

Abstract: The in vitro aromatization and 5alpha-reduction of androgens to estrogens and dihydrotestosterone (DHT) were determined in incubations of microdissected brain regions of male and female gonadectomized, adrenalectomized rats. Metabolites formed from [1alpha,2alpha-3H]androstenedione or [1alpha,2alpha-3H]testosterone were purified by celite liquid-liquid partition chromatography, silica gel chromatography and recrystallization to stable 3H/14C ratios. The medial preoptic nucleus-anterior hypothalamic nucleus exhibited the highest aromatase activity and the second highest conversion to DHT. The lateral preoptic and lateral hypothalamic nuclei showed little aromatase activity yet exhibited high rates of formation of DHT. The medial basal hypothalamus showed the second highest level of aromatase activity but consistently formed the lowest amount of DHT. The discrect anatomical localization of these enzymatic conversions is suggestive of their being involved in the physiological actions of androgens.

Effects of Starvation in Rats on Serum Levels of Follicle Stimulating Hormone, Luteinizing Hormone, Thyrotropin, Growth Hormone and Prolactin; Response to LH-Releasing Hormone and Thyrotropin-Releasing Hormone

Abstract: Adult male Sprague-Dawley rats averaging 300 g each were subjected to complete food removal for 7 days (acutely starved), 7 days complete food removal followed by 2 weeks of ¼ ad libitum food intake (chronically starved), 7 days complete food removal and 2 weeks of ¼ ad libitum intake followed by ad libitum feeding for 7 days (refed), or fed ad libitum throughout (controls). Serum LH, FSH, TSH, PRL, and GH levels were measured by radioimmunoassays for each group of rats. The in vivo response to the combination of synthetic LHRH and TRH also was tested in each group. Circulating LH, TSH, GH, and PRL were significantly depressed in acutely and chronically starved rats, and FSH was lowered only in acutely starved rats. After 7 days of refeeding, serum levels of LH and FSH were significantly greater than in ad libitum fed controls, PRL returned to control levels, and TSH and GH increased but were still below control levels. After LHRH + TRH injection serum LH and TSH were increased significantly in all groups...

Presence of corticotropin in brain of normal and hypophysectomized rats.

Abstract: Immunoreactive and bioreactive corticotropin (ACTH-like) activities have been detected in the median eminence and remaining medial basal hypothalamus of both normal and hypophysectomized adult male rats: bioreactive ACTH (pg/100 mug of protein) 1028 in median eminence and 1289 in medial basal hypothalamus; immunoreactive ACTH (midportion ACTH antibody), 1554 in median eminence and 1887 in medial basal hypothalamus. By use of appropriate antibodies and bioassay, it was demonstrated that immunoreactivity was not due solely to alpha-melanotropin, which has previously been reported to be present in the brain of hypophysectomized animals. The Sephadex G-50 gel filtration patterns determined by immunoassay of column eluates obtained from hypothalamic extracts of normal or hypophysectomized animals were similar but were not identical to the pattern derived from whole pituitary. Immunoreactive (midportion ACTH antibody) ACTH concentrations (pg/100 mug of protein) of other central nervous system areas in normal animals were: cerebellum 34.3, cortex 46.3, thalamus 23.8, and hippocampus 116.3. The total amount of bioreactive ACTH present in the median eminence and medial basal hypothalamus is approximately 1% of that present in the pituitary. The present data suggest that such ACTH may have a diencephalic rather than pituitary origin and raise the question of the functional significance of such ACTH.

Suppression of feeding and drinking activity in rats following intraventricular injection of thyrotropin releasing hormone (TRH).

Abstract: Since both TRH and somatostatin (SRIF) are localized to the ventromedial hypothalamic nucleus, a region known to be involved in control of food intake, the possibility that these peptides might alter food intake was evaluated. The peptides were dissolved in 0.9% NaCl and injected into the 3d ventricle in a volume of 2 micron1 in animals bearing 3d ventricular cannulae. Food and water had been removed from the cages the night before and the intake was measured at 1 and 6 h after injection. Control injections of 0.15M NaCl or glutathione (3 nmoles) had no effect on food or water intake. At a dose of 3 nmoles, LHRH, SRIF, and TRH suppressed water intake alh. Lowering the dose of LHRH and SRIF to 0.6 nmoles led to loss of this inhibition but the suppressive effect of TRH, which was more pronounced at the higher dose than that of the other two peptides, persisted. Lowering the dose of TRH to 0.3 nmoles led to loss of the inhibitory effect. The dose of 3 nmoles of LHRH did not suppress food intake but this dose of both SRIF and TRH had a significant suppressive effect on food intake at 1 h. There was no suppressive action of a lower dose of 0.6 nmoles of SRIF, but TRH was still effective to suppress food intake at this dose. A dose of 0.3 nmoles of TRH had no effect on food intake. It is suggested that TRH, and possibly SRIF may play a physiological role in control of food intake, perhaps by altering the neural activity within the ventromedial nucleus.

Analysis of the disruption in hypothalamic-pituitary regulation in rats treated neonatally with monosodium L-glutamate (MSG): evidence for the involvement of tuberoinfundibular cholinergic and dopaminergic systems in neuroendocrine regulation.

Abstract: Adult rats which have received monosodium-L-glutamate (MSG) (4 mg/g body weight) on alternate days for the first ten days of life acquire neurotoxic lesions of the retina and arcuate nucleus and manifest an endocrine deficiency syndrome characterized by stunted growth, obesity, hypothyroidism, hypogonadism and pituitary atrophy. In the present study, the biochemical basis for the MSG-induced endocrine dysfunction has been examined and the findings of note are as follows: normal serum levels of TSH and LH despite hypothyroidism and gonadal atrophy, and significantly reduced serum GH levels in both males and females; elevated serum PRL levels in males, but not females; normal or augmented pituitary release of LH and TSH to exogenous LHRH and TRH. Within the central nervous system: a normal diurnal rhythm of pineal N-acetyltransferase activity despite optic atrophy; normal concentrations of LHRH, TRH and somatostatin within the medial basal hypothalamus; normal concentrations of norepinephrine (NE), choline ...

Abnormalities in reproductive function associated with the destruction of the suprachiasmatic nuclei in female rats.

Abstract: Extensive lesions of the suprachiasmatic nuclei result in failure of ovulation in the female rat. Damage to adjacent structures (optic chiasma, anterior pole of the arcuate nuclei, anterior hypothalamus, preoptic area) is neither necessary nor, in itself, sufficient to cause failure of ovulation. All anovulatory animals showed a high level of sexual receptivity and some ovulated after mating but few became pregnant. There was no consistent relation between the incidence of ovulation after mating or after progesterone administration and the occurrence of a facilitation of gonadotrophin secretion by progesterone administration to oestrogen-primed animals after ovariectomy. Nor could these responses be correlated with the extent or anatomical location of the lesions. It is suggested that the failure of ovulation may be related to the abolition or disruption of the normal diurnal variation in sensitivity to the facilitatory effects of ovarian steroid hormones.

Prolactin-like immunoreactivity: localization in nerve terminals of rat hypothalamus.

Abstract: Antibodies to rat prolactin were used in immunohistochemical studies of the hypothalamus and preoptic area of the rat. Evidence was obtained that a protein immunochemically related to prolactin was stored in networks of nerve terminals of many hypothalamic areas such as the arcuate nucleus, the dorsomedial hypothalamic nucleus, and periventricular regions of the hypothalamus and preoptic area. The neuronal storage of a prolactin-like protein in the hypothalamus was unaffected by hypophysectomy.

Regulation of prolactin release by endogenous opiates.

Abstract: ENDORPHINS, the endogenous peptides recently isolated and identified in brain have been implicated in regulation of pain1–4. But their wide distribution throughout the brain5–7 and their profound behavioural effects after central administration8 suggest an involvement in other central nervous system processes. Immunohistochemical identification of these endorphins (refs 9, 10 and F. Bloom, personal communication) in hypothalamic neurones indicated that neuroendocrine effects are probable. Morphine was previously reported to block ovulation, while more recently, morphine11 and endorphins12–14 were observed to stimulate release of prolactin and growth hormone. Yet, these observations have not established a direct, tonic participation of endorphins in hypothalamic and anterior pituitary function. The absence of any direct action of opiate antagonists has been taken as an argument against any tonic role of endorphins. Recent reports indicate, however, that opiate antagonists do modify on-going central processes. For example, naloxone and naltrexone lower pain threshold in appropriate conditions in man and experimental animals15–18. Using naltrexone as a tool to block opiate receptor function, we have explored whether endorphins are tonically involved as a putative neurotransmitter in the regulation of prolactin release. The results presented here demonstrate a new instance where an opiate antagonist modifies normal function. The data agree with a preliminary report indicating that naloxone reduced prolactin release in immature female rats19.

Brain Cell Nuclear Retention of Testosterone Metabolites, 5α-Dihydrotestosterone and Estradiol-17β, in Adult Rats

Abstract: Radioactivity was analyzed in tissue homogenates and purified cell nuclear fractions in the pituitary and 9 brain regions 2 h after an iv [7-3H]testosterone infusion into gonadectomizedadrenalectomized adult male and female rats. Unchanged testosterone (T) and its metabolites, 5αdihydrotestosterone (DHT) and estradiol-17β (E2), were the predominant steroids recovered from cell nuclear fractions in all brain regions examined. Highest levels of E2 as a T metabolite were found in nuclear fractions from the amygdala, followed by the hypothalamus, preoptic area and septum, while levels of DHT as a T metabolite were highest in nuclear fractions from the pituitary, followed by the hypothalamus and the septum. The regional pattern was similar in both sexes. Low levels of DHT and E2 recovered from serum indicated these metabolites were probably formed in situ. Regional distributions of cell nuclear retained DHT and E2 as T metabolites were compared with the respective regional distributions observed after either [...

Alterations in basal and TRH-stimulated serum levels of thyrotropin, prolactin, and thyroid hormones in starved obese men.

Abstract: To investigate further the alterations in pituitary-thyroid function seen during starvation, we have measured basal and TRH-stimulated serum levels of thyrotropin (TSH), prolactin (PRL), growth hormone, thyroxine (T4), triiodothyronine (T3), free T4, free T3, and reverse T3 during prolonged fasting in seven obese men. Fasting was associated with a significant decrease in serum (4, (3, and free T3, while there was an increase in serum reverse T3; these values tended to return toward pre-fast levels as the fast continued beyond 3 weeks. No significant changes were seen in basal serum TSH, PRL, growth hormone, or free T4. Although the TSH response to TRH was diminished during fasting, PRL, T4, and T3 responses were unchanged. In addition to transient alterations in the peripheral metabolism of T4, these findings suggest that alterations in the thyroid hormone binding capacity of serum carrier proteins may occur during fasting. The blunted TSH response to TRH despite reduction of serum T3 concentration suggests that subtle alterations in hypothalamic-pituitary function may also occur.

Immunocytochemical localization of the vasopressinergic and the oxytocinergic neurons in the human hypothalamus.

Abstract: The human hypothalamic-neurohypophysial hormone-producing nuclei were investigated with the unlabeled antibody peroxidase-antiperoxidase complex (PAP) technique at the light microscopic level. The size, shape and location of the supraoptic, paraventricular, accesssory supraoptic and suprachiasmatic nuclei were determined. It was demonstrated in the human hypothalamus, as well as in the hypothalamus of other mammals, that vasopressin and oxytocin are synthesized in separate neurons. In each of the nuclei of the magnocellular neurosecretory system, the distribution, ratios and structural features of the vasopressinergic and oxytocinergic neurons were determined. It was shown that the human suprachiasmatic nuclei contain numerous neurophysin-vasopressin-producing neurons.

Dynamics and mechanics of corticosteroid feedback at the hypothalamus and anterior pituitary gland.

Abstract: Corticosteroid feedback mechanisms were investigated at the hypothalamic level using the rat hypothalamus in vitro and the pituitary level using basal hypthalamic-lesioned rats. Both fast and delayed corticosteroid feedback effects were demonstrated at the level of the hypothalamus and pituitary gland with doses of corticosteroids within or near the physiological range. These two phases of feedback were separated temporally by a 'silent period' during which no feedback was apparent. Studies on the mechanism of action of corticosteroids at the hypothalamic level showed that the fast feedback mechanism acts by inhibition of release whilst the delayed feedback mechanism acts by inhibition of both synthesis and release. The fast feedback action of corticosterone does not appear to act by excitation of neuroinhibitory pathways since neither picrotoxin nor phentolamine prevented the feedback action of corticosteroids in vitro. Corticosterone inhibition of corticotrophin releasing factor release was overcome by depolarization of the membrane with K+ suggesting that the mechanism of action of the fast feedback of corticosteroids is by membrane stabilization.

Circadian periodicities of serum androgens, progesterone, gonadotropins and luteinizing hormone-releasing hormone in male rats: the effects of hypothalamic deafferentation, castration and adrenalectomy.

Abstract: Serum testosterone (T), dihydrotestosterone (DHT), progesterone (P), LH, FSH and luteinizing hormone-releasing hormone (LHRH) levels and the LHRH content in the medial basal hypothalamus (MBH) and preoptic area (POA) were estimated during a 24-h period. Circadian rhythms, temporally unrelated to each other, were evident in serum FSH and LHRH and the MBH LHRH content; serum LH fluctuated randomly. In addition, serum T and DHT demonstrated a parallel circadian pattern while serum T and P appeared inversely related. Serum P rhythm persisted in long-term castrate males. Without adversely affecting serum LH, anterior hypothalamic deafferentation abolished both serum T and P rhythms, whereas adrenalectomy obliterated only the serum T periodicity. These studies show that the POAMBH complex and the adrenals play important roles in the circadian regulation of testicular secretions.

The Effects of Adrenalectomy and Glucocorticoid Replacement on Vasopressin and Vasopressin-Neurophysin in the Zona Externa of the Median Eminence of the Rat

Abstract: Adrenal regulation of the vasopressincontaining fibers to the portal capillary system in the zona externa of the median eminence was studied in the rat. Tissue sections of the hypothalamus were examined by immunoperoxidase technique and light microscopy using antisera to oxytocin and arginine vasopressin, and an antiserum which reacts with all rat neurophysins. These peptides were localized in the intact normal rat and after adrenalectomy, glucocorticoid replacement with dexamethasone, and after dehydration. The effect of adrenalectomy was also examined in the homozygous Brattleboro rat with diabetes insipidus (DI rat) which lacks arginine vasopressin and, arginine vasopressinneurophysin. In the zona externa of the normal rat a small number of arginine vasopressin and neurophysin- containing fibers, and an occasional one containing oxytocin were traced to the portal capillary bed. The zona externa of the unoperated DI rat contained only an occasional neurophysin- and oxytocin-reactive fiber. In the normal...

The distribution of luteinizing hormone-releasing hormone (LHRH) in the hypothalamus of the rhesus monkey. Light microscopic studies using immunoperoxidase technique.

Abstract: Neural structures containing LHRH were characterized in the hypothalamus of the rhesus monkey by four different antisera to the hormone and an immunoperoxidase technique. Immunoreactive perikarya were present in a continuum from the septal-preoptic region anteriorly to the premammillary nucleus posteriorly. These cells were more concentrated in the pericommissural and tubero-infundibular regions. Reactive axons in the median eminence appeared to originate from the positive perikarya in the medial basal hypothalamus; this projection forms a tubero-infundibular tract containing LHRH. In addition, substantial numbers of fibers which entered the median eminence continued down the infundibular stalk and into the posterior pituitary. Other axons appeared to originate in the pericommisural region and projected to the organum vasculosum of the lamina terminalis. Scattered positive fibers were also present in other hypothalamic areas, especially in the periventricular zone and medical mammillary nucleus.