Showing papers on "Hypothalamus published in 1970"

PRODUCTION OF BOTH PROLACTIN AND GROWTH HORMONE BY CLONAL STRAINS OF RAT PITUITARY TUMOR CELLS Differential Effects of Hydrocortisone and Tissue Extracts

Abstract: Several established clonal strains of rat pituitary cells which produce growth hormone in culture have been shown to secrete a second protein hormone, prolactin. Prolactin was measured immunologically in culture medium and within cells by complement fixation. Rates of prolactin production varied from 6.6 to 12 µg/mg cell protein per 24 hr in four different cell strains. In these cultures ratios of production of prolactin to growth hormone varied from 1.0 to 4.1. A fifth clonal strain produced growth hormone but no detectable prolactin. Intracellular prolactin was equivalent to the amount secreted into medium in a period of about 1–2 hr. Both cycloheximide and puromycin suppressed prolactin production by at least 94%. Hydrocortisone (3 x 10-6 M), which stimulated the production of growth hormone 4- to 8-fold in most of the cell strains, reduced the rate of prolactin production to less than 25% of that in control cultures. Conversely, addition of simple acid extracts of several tissues, including hypothalamus, to the medium of all strains increased the rate of production of prolactin six to nine times and decreased growth hormone production by about 50%. We conclude that multifunctional rat pituitary cells in culture show unusual promise for further studies of the control of expression of organ-specific activities in mammalian cells.

Stimulation of Human-Growth-Hormone Secretion by L-Dopa

Abstract: The effect of L-dopa, a precursor of Central-nervous-system catecholamines, on growth-hormone secretion was studied in a group of patients with Parkinson's disease undergoing treatment with the drug. Oral doses (0.5 g) caused a significant rise in plasma growth hormone in patients initially starting therapy or on chronic therapy for as long as 11 months. The rise in plasma growth hormone persisted for 120 minutes after the administration of the drug. The L-dopa-induced rise in plasma growth hormone could not be blocked by either oral or intravenous glucose administration. The data suggest that a dopaminergic mechanism in the median eminence or a norepinephrine-sensitive site in the hypothalamus or limbic system may be involved in the regulation of growth-hormone secretion. Furthermore, patients with Parkinson's disease, on L-dopa therapy, appear to be under the influence of elevated plasma growth hormone for a substantial part of the day.

Effect of Anterior Pituitary Perfusion and Intraventricular Injection of Catecholamines and Indoleamines on LH Release

Abstract: The median eminence, pituitary stalk and anterior pituitary as well as the adjacent diencephalon were exposed through a parapharyngeal approach to enable us to visualize these structures directly and to inject isotonic salt solutions containing dopamine, epinephrine, norepinephrine, serotonin or melatonin into the third ventricle, a stalk portal vessel or the basilar artery of anesthetized male rats. The rate of LH release in these animals was evaluated from the changes in the concentration of serum LH as determined by radioimmunoassay. Within 10 min after 1.25 μg of dopamine hydrochloride was injected into the third ventricle, the serum LH concentration had increased 4-fold. After 20 min, the serum LH level had increased 9-fold. At 30 and 60 min after the injection, there was a moderate decline followed by a steady rise for at least 1 hr. At the end of the 120-min observation period, the serum LH level was 20 times greater than that of the control animals which received an isotonic salt solution only. Fo...

Failure of 5α-Dihydrotestosterone to initiate Sexual Behaviour in the Castrated Male Rat

Abstract: IN most mammalian species the principal steroid product of the testes is testosterone, 17α-hydroxyandrost-4-en-3-one. In addition to being one of the most potent naturally occurring androgens it has been considered to be the active form of the hormone at target tissue level. Recent reports suggest, however, that a metabolite of testosterone, 17α-hydroxy-5-androstan-3-one (5α-dihydrotestosterone (5α-DHT)), may be the active form of the hormone1,2. Several target organs (prostate, seminal vesicle and penis) rapidly convert testosterone to 5α-DHT (refs. 1 and 2). This conversion occurs before the attachment of the hormone to the receptors3 and seems to be essential for subsequent protein synthesis. Additional evidence for this function of 5α-DHT comes from studies on patients with testicular feminization; tissue biopsies from the genital organs of such patients cannot convert testosterone to 5KDNT (ref. 4). Testosterone can also activate both male and female sexual behaviour and is more potent than oestrogens in inducing libido in women5. Recently the enzyme system needed to convert testosterone to 5α-DHT has been demonstrated in the hypothalamus of the rat and dog6,7, which suggests that 5α-DHT may also be the active form of testosterone in inducing sexual behaviour. In the ovariectomized female rabbit, however, 5α-DHT is devoid of any oestrus-inducing properties at doses from 2–20 mg per day8. 5α-DHT cannot be converted to oestrogenic metabolites in vivo9, which suggests that the aromatization of androgens may be of significance in the activation of sexual behaviour. This preliminary report concerns the failure of 5-DHT to initiate sexual behaviour in the castrated male rat.

Reciprocal Hunger-Regulating Circuits Involving Alpha-and Beta-Adrenergic Receptors Located, Respectively, in the Ventromedial and Lateral Hypothalamus

Abstract: The injection of adrenergic and adrenolytic drugs directly into the brain through permanently implanted cannulas has yielded results showing that food consumption in the rat is regulated by a hypothalamic alpha-adrenergic „hunger” system. and a hypothalamic beta-adrenergic „satiety” system. The rats' differential responses to alpha-adrenergic and beta-adrenergic drugs injected into different hypothalamic sites indicate the following: (1) the lateral hypothalamic „feeding” center contains beta receptors, the activation of which produces satiation, presumably by inhibition of the lateral „feeding” cells; (2) the ventromedial hypothalamic „satiety” center contains alpha receptors, the activation of which produces eating, presumably by inhibition of the ventromedial „satiety” cells; and (3) the medio-lateral perifornical area of the hypothalamus contains both alpha and beta receptors, which lead to inhibition of the ventromedial or lateral hypothalamic centers respectively. It is suggested that the ventromedial and lateral hypothalamus are connected by reciprocal circuits, so that activation of the ventromedial center results in stimulation of the lateral beta receptors which inhibit the lateral „feeding” cells, and activation of the lateral center results in stimulation of the ventromedial alpha receptors which inhibit the ventromedial „satiety” cells.

Prolactin and Growth Hormone Production as Influenced by Catecholamines and Agents that Affect Brain Catecholamines

Abstract: The in vitro influence of dopamine on the in vitro incorporation of leucine-4,5-3H into rat pituitary gland prolactin and growth hormone was studied. This catecholamine primarily inhibited

Changes in Multiple Unit Activity of the Brain During the Estrous Cycle

Abstract: Electrical activity of the brain during the critical period in the rat was examined throughout the estrous cycle, using chronically implanted macro-micro electrodes. Slight circadian rhythms were observed in the basal level of the integrated multiple unit activity (MUA) in the basal hypothalamus and forebrain limbic area. In addition to these changes, a gradual increase of MUA in the basal hypothalamus was observed during the evening of diestrus day 2, while there was no change in the forebrain limbic preoptic area. However, a characteristic elevated pattern of MUA appeared for 12 to 25 min during the critical period (2 p.m. to 4 p.m.), both in the basal hypothalamus and forebrain limbic preoptic area, i.e., in the arcuate nucleus (ARC), ventromedial hypothalamic nucleus (VMH), medial preoptic area (MPO), septum (SEPT), amygdala (AMYG) and bed nucleus of stria terminalis (BST). The episodes of the characteristic pattern were also observed in the basal hypothalamus on the afternoons of diestrus day 2 and estrus, as well as in the forebrain limbic preoptic area on the day of estrus. To determine the possible relationship between the characteristic pattern and gonadotrophin release, electrochemical stimulation was applied to the areas of the brain where the characteristic pattern was observed during the critical period. Ovulation could be induced by stimulation of the ARC, MPO, SEPT, AMYG, and BST, but not by stimulation of the reticular formation (RF) and hippocampus (HPC). Furthermore, the results shed light on the facilitatory and inhibitory effects of progesterone on ovulation and the onset of the critical period.

Serum Prolactin Levels in Rats with Pituitary Transplants or Hypothalamic Lesions

Abstract: Serum prolactin levels were determined by radioimmunoassay in hypophysectomized, ovariectomized rats bearing 0, 1, 2, or 4 anterior pituitaries (AP) underneath the kidney capsule at 1, 2, 4, 6, 8, and 10 weeks after transplantation. Rats with no AP transplants had barely detectable levels of serum prolactin, whereas rats with 1 AP transplant from female cycling rats had serum prolactin values as high as those seen in estrous rats (120 ng/ml serum). In rats bearing 2 AP transplants, serum prolactin increased to 170 ng/ml serum, whereas 4 AP transplants elevated serum prolactin to 250 ng/ml, which is about equivalent to that in lactating postpartum rats (280 ng/ml). Injections of estradiol benzoate (1 µg/day for 5 days) into rats bearing 0, 1, 2, or 4 AP transplants, beginning 10 weeks after transplantation, increased serum prolactin over pre-treatment levels, except in the rats with no pituitary transplants. Bilateral lesions placed in the median eminence or anterior hypothalamus of ovariectomized rats significantly increased serum prolactin to 125 and 85 ng/ml, respectively, as compared with sham-lesioned controls (20 ng/ml). Posterior hypothalamic lesions increased serum prolactin concentration slightly and lesions in the amygdaloid nuclei had no effect. These results indicate that removal of hypothalamic inhibition of prolactin release by pituitary transplantation or by appropriate lesion placement in the hypothalamus results in elevated serum prolactin levels.

Growth hormone dynamics in acromegaly.

Abstract: Patterns of growth hormone response to the provocative stimuli of insulininduced hypoglycemia, arginine infusion and exercise, and to the suppressive effects of hyperglycemia were studied in acromegalic subjects in order to examine the frequency of autonomous behavior of these functioning pituitary tumors. In all but one instance, non-autonomous behavior of growth hormone secretion characterized these acromegalic subjects. Persistence of a given pattern to particular physiologic manipulations indicated that such alterations in growth hormone levels were not random secretory discharges. Non-autonomous behavior of growth hormone secretion in active acromegaly would seem to imply hypothalamic control of growth hormone secretion despite elevated levels of growth hormone in these patients. These observations and the frequency with which unusual or paradoxical growth hormone responses were obtained suggest the possibility that acromegaly may begin as a primary hypothalamic disturbance with chronically ...

Ultrastructural changes in the median eminence of the rat following deafferentation of the basal hypothalamus.

Abstract: This report concerns a light and electron microscopic investigation of the median eminence and dorsal infundibular stem of the rat following surgical isolation (deafferentation). Using a modification of the Halasz technique, the basal hypothalamus, including the arcuate nucleus and median eminence were surgically isolated from surrounding structures. Special attention was directed to the contact (external) zone of the median eminence and rostral infundibulum where tuberohypophyseal axons as well as ependymal cell processes abut upon the abluminal basement membrane of the portal perivascular space. The results of this study to date suggest that 9, 20, and 40 days following surgical isolation, there is a distinct increase in the population of tuberohypophyseal dense core vesicles. It is suggested that deafferentation abolishes inhibitory and excitatory input that serves to modify the cellular dynamics of tuberohypophyseal neurosecretory elements. Comments are also made on the presence of cistern-like structures in the lateral median eminence; the presence of vesicle-like inclusions in terminal ependymal processes is discussed in relationship to the role that ependyma may play in linking the third ventricle with the adenohypophysis.

3H-Estradiol: In Vitro Binding to Macromolecules from the Rat Hypothalamus, Anterior Pituitary and Uterus

Abstract: The in vitro interaction of 3H-estradiol with macromolecules from various organs was studied. Tissues from ovariectomized rats were homogenized in Tris-HCl containing EDTA and radioactive estradiol mixed with the 100,000 × g supernatants. After incubation macromolecular bound radioactivity was separated by gel filtration. Higher concentrations of radioactive estradiol were found in the macromolecular fractions from the hypothalamus, anterior pituitary and uterus than from the cerebrum, cerebellum, heart or plasma. The binding molecules from the hypothalamus, anterior pituitary and uterus were found to have the following properties. Nonradioactive estradiol (10−7m) reduced binding, whereas progesterone or testosterone (10−5m) did not. Intravenous injection of nonradioactive estradiol decreased subsequent binding of 3H-estradiol in vitro. The binding molecules contain protein and appear to have sulfhydryl groups that influence the interaction with estradiol. (Endocrinology 86: 1313, 1970)

Adrenergic blockade and the corticosteroid and growth hormone responses to methylamphetamine.

Abstract: THE observation that the hypothalamus has a high concentration of adrenergic neurones1 and the highest catecholamine content of any central nervous system structure2 has focused attention on the possible role of central catecholamines in neuroendocrine regulation. In a previous study3 we have shown that the sympathomimetic and central stimulant drugs dextro- and methylamphetamine cause significant elevation of plasma corticotrophin, corticosteroids and growth hormone levels in human subjects. The rise in corticosteroids is most pronounced in the evening. It seems likely that the amphetamines act either directly on the hypothalamic neurones responsible for secretion of pituitary hormone releasing factors, or that they result in the local accumulation of catecholamines which then cause these neurones to secrete.

Role of catecholamines in stimulating the release of pituitary ovulating hormone(s) in rats.

Abstract: This study tests the hypothesis that changes in the dynamics of depletion of hypothalamic catecholamines (CA) may affect the stimulation of ovulation. Partial as well as total depletions of CA were attempted by appropriately timed injections of reserpine and inhibitors of monoamine-oxidase. Treatment with reserpine in the morning of proestrus inhibited spontaneous ovulation and elevated the electrical threshold of the medial preoptic area but did not alter the threshold for inducing ovulation by stimulating the median eminencearcuate nucleus region. At high levels of current both areas responded similarly with stimulation of ovulation. Complete blockade of the electrically stimulated release of ovulating hormone was obtained 18–20 hr after treatment with reserpine. However, even after this prolonged reserpine action inhibitors of monoamine-oxidase restored enough CA to support electrically stimulated but not spontaneous ovulation. Infusions into the third ventricle indicated that CA act as neural triggers...

Location of the Neural Structures Triggering Ovulation in the Rat

Abstract: The present studies concerned the location of the neural structures triggering ovulation. Using a small bayonet-shaped knife, three types of deafferentation were made and the rats were tested for ovul

Effects of Central Acting Drugs on Serum and Pituitary Prolactin Levels in Rats

Abstract: A single intraperitoneal injection of reserpine (R), chlorpromazine (C), alphamethyl- para-tyrosine (AMPT) or alpha-methylmeta-tyrosine (AMMT) in proestrous rats produced profound elevations in serum prolactin 30 min to 4 hr after injection. R, C and AMPT decreased pituitary prolactin concentration, whereas AMMT increased it. This indicates that these 4 drugs evoked rapid release of prolactin from the pituitary, and that AMMT also elicited rapid synthesis of prolactin. The increased release of pituitary prolactin may be related to inhibition by the drugs of catecholamine activity in the hypothalamus and/or to reduced hypothalamic PIF content. A single intraperitoneal injection of dopamine (D), epinephrine (E), norepinephrine (NE) or serotonin (S) had no significant effect on serum prolactin levels 1 or 2 hr after injection. D, E and NE also had no effect on serum prolactin values when injected intracarotidly. The higher doses of E and D but not NE produced a small decrease in pituitary prolactin concentra...

Hypothalamic Stimulation of Growth Hormone and Thyrotropin Release in Vitro and Pituitary 3′5′-Adenosine Cyclic Monophosphate1

Abstract: Studies of the effects of hypothalamic extracts and aminophylline on growth hormone (GH) and thyrotropin (TSH) release and tissue cyclic-AMP concentrations in vitro were carried out. Crude hypothalamic extracts were found to increase release of both hormones and to increase pituitary cyclic-AMP concentration. Greater effects were found with increasing amounts of SME and aminophylline. A close correspondence existed between the time at which elevated tissue cyclic-AMP levels and stimulation of hormone release was observed. Furthermore, doses of hypothalamic extract and aminophylline that failed to stimulate hormone release also failed to increase tissue cyclic-AMP concentrations. Hypothalamic extracts were found to stimulate pituitary adenyl cyclase activity without affecting pituitary cyclic-AMP phosphodiesterase activity. Removal of calcium from the incubation medium diminished release of TSH and GH in response to SME and aminophylline, but had no effect on pituitary cyclic- AMP concentration. These resu...

The hypothalamus and control of ovulation.

Abstract: The authors review evidence that the central nervous system (CNS) is directly concerned with the ovulatory process. They discuss the effects of environmental influences on ovulation. There is evidence in many animals that day-night changes produce changes in ovulation. The menstrual rhythm of the human female is influenced by emotional and environmental factors. 12 hours before ovulation a stimulus passes from the CSN to the anterior pituitary which causes a surge in secretion of LH (luteinizing hormone). When lesions are placed on the hypothalamic site of stimulation ovulation is blocked. Various releasing factors are liberated from nerve endings of the hypothalamic nerve tracts into the primary plexus of capillaries of the hypophysial portal vessels in the median eminence. The releasing factors are carried into the gland where they regulate the secretion of the anterior pituitary hormones. The authors also discuss feedback actions of the ovarian steroid hormones via CNS which influence ovulation.

Effect of Lesion Size in the Ventromedial Hypothalamus on Growth Hormone and Insulin Levels in Weanling Rats

Abstract: Electrolytic lesions of three different sizes were placed in and around the ventromedial hypothalamic nuclei (VMN) in weanling rats. After three weeks, during which food intake was measured, the rats were killed and the following parameters were measured: plasma growth hormone (GH), insulin and glucose, carcass fat, water and lean body mass, pituitary weight and GH content, and ponderal and linear growth. Progressive decreases in pituitary weight, pituitary and plasma GH, linear growth, and carcass water and lean body mass were produced by increasing lesion size. Concomitant increases occurred in plasma insulin and carcass fat. Ponderal growth and plasma glucose were unaffected by any of the lesions and none of the experimental groups exhibited hyperphagia. The data indicate that the VMN are a control site for GH and insulin secretion. The lack of correlation between parameters of growth and those of obesity suggests that the two hormonal control mechanisms are subserved by independent neuronal assemblies.

Central monoamine neurons and pituitary-adrenal activity.

Abstract: Publisher Summary To elucidate the role of central monoamine neurons in the regulation of pituitary-adrenal activity, experiments have been started to study the amine turnover in central monoamine neurons in endocrine states with various degrees of adrenocorticotropic hormone (ACTH) secretion. NA neurons may exert an inhibitory influence that, at least in certain situations, could be of importance for the regulation of ACTH secretion. This interpretation is supported by the fact that steroid-sensitive neurons in the hypothalamus are, to a large extent, inhibited by NA. The central 5-hydroxytryptamine (5-HT) neurons probably do not directly participate in ACTH regulation with regard to stress responses. However, the 5-HT neurons may still play a role in the regulation of ACTH secretion, since 5-HT turnover is reduced by adrenalectomy and restored again to normal by subacute treatment with glycocorticoids. The increased 5-HT turnover caused by prolonged treatment with glycocorticoids may be of importance both for the negative feedback action on ACTH secretion caused by these steroids and for their actions on the affective state.

Adipose tissue metabolism of weanling rats after destruction of ventromedial hypothalamic nuclei: Effect of hypophysectomy and growth hormone

Abstract: This report describes the effects of hypophysectomy and growth hormone treatment on the endocrine-metabolic alterations associated with destruction of the ventromedial hypothalamic nuclei (VMN) in weanling rats. In addition to previously noted characteristics of the syndrome (increased plasma insulin and triglyceride levels without hyperphagia, normal plasma glucose, and decreased plasma growth hormone levels with impaired linear growth), changes in in vitro adipose tissue metabolism of glucose-U-C 14 and palmitate-1-C 14 were observed. Glucose oxidation and incorporation into lipid were markedly elevated, whereas palmitate oxidation was decreased in adipose tissue of VMN rats. Although hypophysectomy and growth hormone treatment alone or in combination produced effects in rats with or without VMN lesions, neither significantly modified the characteristic changes observed in untreated rats with VMN lesions.

Effects of cations on prolactin and growth hormone secretion by rat adenohypophyses in vitro

Abstract: 1. Explants of rat adenohypophyses were incubated in medium 199, Earle's saline, or modified Earle's saline (K-Earle's) with different calcium, magnesium, sodium and potassium concentrations for 4-6 hr at 37 degrees C in 5% CO(2) in O(2).2. The amount of prolactin and growth hormone in explants and in medium was estimated by disk electrophoresis and densitometry.3. Low calcium inhibited prolactin secretion by 40-60%. Low magnesium and slightly increased (5x) magnesium (4.1 mM) did not influence prolactin secretion in either 1.8 mM or low calcium, but 10 and 20 mM magnesium inhibited secretion by 50 and 70%, respectively. Inhibition of prolactin secretion by high magnesium was reversible.4. Decreasing sodium by 80% had no effect on prolactin secretion, but low sodium inhibited the sustained, although not acute, secretion of this hormone.5. Low potassium did not affect the secretion of either prolactin or growth hormone. Increased potassium (32 or 54 mM) slightly stimulated prolactin secretion by adenohypophyses of males but had no effect on the secretion of this hormone by female glands.6. In 1.8 mM calcium, growth hormone secretion by pituitaries of males and females was markedly stimulated by increased potassium, but it was not appreciably affected by high potasium in low calcium. Increased potassium did not stimulate growth hormone secretion in medium containing low sodium with normal calcium.7. Secretion of prolactin and growth hormone by rat adenohypophyses is dependent upon calcium, but only growth hormone secretion is markedly stimulated by increased potassium. The difference in responsiveness to increased potassium, between the somatotrophs and lactotrophs, may be related to the predominant mode of hypothalamic control of these hormones.

Monoamine oxidase activity in the hypothalamus and various other brain areas and in some endocrine glands of the rat during the estrus cycle12

Abstract: —The activity of monoamine oxidase (MAO, EC 1.4.3.4) was measured in the entire hypothalamus and different hypothalamic regions, in the amygdala, frontal and lateral cerebral cortex, in the pituitary, adrenals and genital organs of male rats and of female rats during the estrus cycle. Activity of MAO changed cyclically in the hypothalamus, amygdala, adrenals and ovaries. The highest levels in the hypothalamus occurred at 10 a.m. on the day of proestrus and during estrus. The lowest levels occurred at 6 p.m. on the day of proestrus, of metestrus and during diestrus. Cyclical variations similar to those found in the whole hypothalamus were also observed in anterior, posterior and lateral portions and the median eminence of the hypothalamus. Activity in the median eminence was greater than that of the whole hypothalamus or its various other portions. The amygdala exhibited less marked cyclical activity which followed the pattern of the hypothalamus by increasing at 10 a.m. and peaking at 3 p.m. on the day of proestrus. At the‘post-critical’period of proestrus, when the activity of MAO in the hypothalamus and amygdala decreased, the activity of MAO in the ovaries and adrenals rose. During the estrus cycle much lower levels of activity of MAO were demonstrated in other regions of the brain (frontal and lateral cerebral cortex), in the pituitary and in the uterus, none of which showed cyclical changes. The changes in activity of MAO in cerebral tissues, endocrine glands and genital organs have been discussed in relation to the probable participation of monoamines in the mechanism(s) of secretion of gonadotrophins by the hypothalamus.