Influence of stress of a maternal organism on the turnover of catecholamines in the brain of early postnatal rats

Effects of prenatal stress (daily 1-h-long immobilization of pregnant females at the 15th–21st days of pregnancy) on the formation of sex-related dimorphism of the turnover of noradrenaline (NA) and dopamine (DA) in the preoptic area (POA) of the brain and mediobasal hypothalamus (MBH) were studied in 10-day-old rats. Sex-related differences of the turnover of a functional NA pool in the POA and DA pool in the MBH were demonstrated in intact control rats: a higher rate of the monoamine turnover was observed in males. Prenatal stress abolished these sex-related differences and, at the same time, induced such differences in the DA turnover in the POA. It is supposed that prenatal stress-evoked early modifications of sex-related dimorphism of the catecholamine turnover in the brain can result in the development of remote disturbances in the neuroendocrine control of reproduction and adaptation.     

Catecholamines in steroid-dependent brain development

Sex-specific peculiarities of catecholamine (CA) content and turnover in neuroendocrine brain areas and their modification with neonatal steroids or prenatal stress (PS) in Wistar rats were studied. No changes in noradrenaline (NA) content and turnover rate were found in the preoptic area (POA), meanwhile dopamine (DA) turnover rates in the POA and mediobasal hypothalamus (MBH) were increased in neonatally androgenized 10-day-old females. Treatment of female neonates with various catecholestrogens increased hypothalamic NA content by 30–95% but only 4-hydroxyestradiol-17β induced anovulation. 6-Hydroxydopamine had no significant impact on hypothalamic CA content in neonates and did not prevent testosterone-induced persistent estrous. Maternal stress (restriction for 1 h a day, 15–21st days of pregnancy) resulted in a decrease of hypothalamic NA and blood plasma corticosterone response to acute stress in adult male offspring. Sex differences in CA content in the POA and MBH disappeared in 10-day-old prenatally stressed rats. Conclusions: (1) sexual brain differentiation needs co-operative actions of sex steroids and CA to be completed; and (2) early changes in CA content and turnover induced by PS or neonatal steroid exposure predetermine long-term alterations of the stress responsiveness, reproductive behaviour and neuroendocrine control of ovulation.     

Prenatal stress and glucocorticoid effects on the developing gender-related brainProceedings of Xth International Congress on Hormonal Steroids, Quebec, Canada, 17–21 June 1998.

Hormonal and neurotransmitter environment of nondifferentiated cells in the developing brain determines many of gender-specific behavioural and neuroendocrine functions. Early postnatal and long-term effects of maternal stress or prenatal glucocorticoid on sex-related peculiarities of the brain morphology, biogenic monoamine turnover, testosterone metabolism, hypothalamic noradrenaline (NA) and adrenocortical responses to an acute stress were studied in Wistar rat offsprings. Maternal stress (1 h immobilization daily for gestational days 15–21) prevented development of sexual dimorphism in neuronal cell nuclei volumes in suprachiazmatic nucleus (SCN) in 10 day old pups. That was associated with a disappearance of male–female differences in NA and 5-hydroxytryptamine turnover in the preoptic area (POA) and dopamine (DA) turnover in the mediobasal hypothalamus (MBH) by decreasing them in male pups. Hydrocortisone acetate (5 mg daily during the last week of pregnancy) produced changes in NA turnover in the POA of males and females which were quite similar to those after maternal stress. Changes in aromatase and 5-reductase activities in the POA of male pups were quite opposite as affected by maternal stress or prenatal glucocorticoid. Sexual differences in 5-reductase activity in the MBH appeared due to its increase in prenatally stressed male pups. In contrast to adult males, in adult females maternal stress did not restrict hypothalamic NA and blood plasma corticosterone response to acute stress (1 h immobilization). Our findings on morphology and functions of gender-related developing brain areas stand in correlation with modifying effects of maternal stress and prenatal glucocorticoid on behavior and neuroendocrine regulations.     

Changes in substance P content at the hypothalamic-pituitary axis during the Wallerian degeneration of peripheral sympathetic neurons after superior cervical ganglionectomy in male rats: effect of hyperprolactinemia

The effects of Wallerian degeneration of the peripheral sympathetic neurons projecting to the hypothalamus on the mechanism of interaction between prolactin and substance P (SP) were examined. The effects of superior cervical ganglionectomy (SCGx) on SP content in various hypothalamic regions and in the hypophysis were evaluated in control and hyperprolactinemic rats. Male rats that received pituitary transplants at the age of 5 days and age-matched sham-operated controls were used. Pituitary grafting significantly increased circulating values of prolactin, as did SCGx. In hyperprolactinemic rats, SCGx partially decreased plasma prolactin levels. Neonatal hyperprolactinemia decreased SP content in the anterior (AH) and posterior (PH) hypothalamus and in the median eminence (ME), but increased it in the mediobasal hypothalamus (MBH). Acute SCGx significantly increased SP in the MBH, PH, and ME. SCGx in hyperprolactinemic animals further increased SP content in MBH. In the ME and Ah, SCGx in pituitary grafted rats decreased SP content as compared with the controls. In the pituitary gland (PG), SCGx only decreased SP content in hyperprolactinemic, but not in control rats. An interaction between peripheral nor-adrenergic neurons and prolactin to regulate SP within the hypothalamus was positive in the MBH, AH, ME, and PG, but not in the PH. These data indicate the existence of interactive mechanisms between prolactin and the peripheral sympathetic neurons to regulate SP content at the hypothalamic-pituitary axis. Interrelationships between prolactin and SP were also observed.     

Influence on Turnover and Level of Hypothalamic Noradrenaline by a New Antihypertensive Agent (GYKI 11679)

Abstract— In an attempt to delineate the possible importance of the concentration of noradrenaline at hypothalamic noradrenergic receptor sites in a hypotensive response to a drug, the action of a new antihypertensive agent, 1-(6-morpholino-3-pyridazynyi)-2-(1-[tert-butoxycarbonyi]-2-propylidene)-diazane (GYKI 11679), on the turnover rate and the endogenous level of noradrenaline (NA) in rat hypothalamus was examined. An effective, antihypertensive i.p. dose of the compound (10 mg/kg) produced a significant but relatively short-lasting reduction in the hypothalamic noradrenaline content, whereas no change was observed in the cardiac catecholamine level. The NA turnover determinations, carried out in GYKI 11679-pretreated rats by measuring the disappearance of labeled NA at 1, 2, 3, and 5 h after the injection of the radioactive amine, showed that a 10 mg/kg i.p. dose of the compound, given 1 h prior to the i.c.v. administration of the labeled NA, increased the turnover rate of noradrenaline to a great extent. The estimated half-lives of NA in the hypothalamus of the treated and of the non-treated animals were calculated as 1.72 and 3.62 h, respectively. In vitro studies showed that the spontaneous outflow of noradrenaline from hypothalamic slices was accelerated by GYKI 11679 in a dose-dependent manner in a concentration range of 10^?5 to 10^?7m . In a 10-fold higher range, GYKI 11679 produced inhibition of both the hypothalamic and the adrenal tyrosine hydroxylase activity but did not alter DOPA-decarboxylase, dopamine-β-hydroxylase, or monoamine oxidase activities. Direct in vivo measurements of catecholamine synthesis by determining the ³H-catecholamines (CA) formed from [³H]tyrosine in the hypothalamus after an i.c.v. administration of the labeled precursor showed a moderate increase in [³H]CA formation following a 10 mg/kg dose of the compound. When GYKI 11679 was administered in a 75 mg/kg i.p. dose to rats, the transformation was reduced by –50%. Adenylate cyclase activity measurements did not show stimulatory or inhibitory actions of the drug on the NA-stimulated adenylate cyclase of the rat hypothalamus, in accordance with previous results. This suggests that the increased NA turnover (utilization) caused by an effective, antihypertensive dose of GYKI 11679 is the direct consequence of an increased outflow, which occurs primarily in the hypothalamus. The increased activity of the noradrenergic neurons in this brain region might lead to a reduced sympathetic activity in the periphery and thus to a significant decrease in blood pressure.     

Impact of proestrous milieu on expression of orexin receptors and prepro-orexin in rat hypothalamus and hypophysis: actions of Cetrorelix and Nembutal

Orexins and their receptors OX1 and OX2 regulate energy balance and the sleep-wake cycle. We studied the expression of prepro-orexin (PPO), OX1, and OX2 in brain and pituitary under the influence of the hormonal status in adult rats. Primarily, PPO, OX1, and OX2 expression was determined in Sprague-Dawley female cycling rats during proestrus and in males. Animals were killed at 2-h intervals. Anterior (AH) and mediobasal (MBH) hypothalamus, anterior pituitary (P), and frontoparietal cortex (CC) were homogenized in TRIzol, and mRNAs were obtained for screening of PPO, OX1, OX2 expression by semiquantitative RT-PCR. Main findings were confirmed and extended to all days of the cycle by quantitative real-time RT-PCR. Hormones and food consumption were determined. Finally, OX1, OX2, and PPO were measured by real-time RT-PCR in tissues collected at 1900 of proestrus after treatments at 1400 with ovulation-blocking agents Cetrorelix or pentobarbital. OX1 and OX2 expression increased at least threefold in AH, MBH, and P, but not in CC, between 1700 and 2300 of proestrus, without variations in estrus, diestrus, or in males. PPO in AH and MBH showed a fourfold or higher increase only during proestrus afternoon. Cetrorelix or pentobarbital prevented increases of OX1 and OX2 only in the pituitary and blunted gonadotropin surges, but left OX1, OX2, and PPO brain expression unchanged. Reproduction, energy balance, and sleep-wake cycle are integrated. Here, we demonstrate that, in the physiological neuroendocrine condition leading to ovulation, information to the orexinergic system acts in hypothalamus and pituitary by different mechanisms.     

Possible role of vasoactive intestinal peptide in the hyperprolactinemia induced by ethanol

The effect of the blockade of endogenous VIP by injecting a specific rabbit anti-VIP serum (A-VIP) was studied in rats receiving an acute injection of ethanol. A-VIP administration decreased serum prolactin levels and reduced the hyperprolactinemia induced by ethanol. We also investigated the effect of the acute administration of ethanol on the concentration and release of VIP from the mediobasal hypothalamus. Ethanol decreased VIP concentration in the mediobasal hypothalamus, whereas it stimulated the in vitro K(+)-evoked release of VIP from this tissue. Conversely, ethanol increased VIP concentration in the anterior pituitary gland. The data indicate that VIP may be involved in the pituitary response to ethanol. The increased anterior pituitary VIP after ethanol may be due to an augmented release from the mediobasal hypothalamus.     

Daily Changes of GABA and Taurine Concentrations in Various Hypothalamic Areas Are Affected by Chronic Hyperprolactinemia

This study was designed to characterize, in anterior, mediobasal, and posterior hypothalamic and median eminence, the 24h changes of gamma aminobutyric acid (GABA) and taurine (TAU) contents in adult male rats and to analyze whether chronic hyperprolactinemia may affect these patterns. Rats were turned hyperprolactinemic by a pituitary graft. Plasma prolactin (PRL) levels increased after pituitary grafting at all time points examined. A disruption of the circadian rhythm was observed in pituitary-grafted rats, whereas GABA and TAU content followed daily rhythms in all areas studied in controls. In the mediobasal hypothalamus, two peaks for each amino acid were found at midnight and midday. In the anterior hypothalamus, GABA and TAU showed only one peak of concentration at midnight. In the posterior hypothalamus, the values of both GABA and TAU were higher during the light as compared to the dark phase of the photoperiod. In the median eminence GABA content peaked at 20:00h, the time when TAU exhibited the lowest values. Hyperprolactinemia abolished the 24h changes of GABA in the mediobasal hypothalamus and reduced its content as compared to controls. Hyperprolactinemia advanced the diurnal peak of TAU to 12:00h in the mediobasal hypothalamus and did not modify the 24:00h peak. In the anterior hypothalamus, hyperprolactinemia increased GABA and TAU contents during the light phase while it decreased them during the dark phase of the photoperiod. In the posterior hypothalamus hyperprolactinemia did not modify GABA or TAU patterns as compared to controls. In the median eminence hyperprolactinemia increased the 20:00h peak of GABA and shift advanced the decrease in TAU content at 20:00h and its maximum at 24:00h as compared to controls. These data show that GABA and TAU content exhibit specific daily patterns in each hypothalamic region studied. PRL differentially affects the daily pattern of these amino acids in each hypothalamic region analyzed.     

Daily changes of GABA and taurine concentrations in various hypothalamic areas are affected by chronic hyperprolactinemia

This study was designed to characterize, in anterior, mediobasal, and posterior hypothalamic and median eminence, the 24h changes of gamma aminobutyric acid (GABA) and taurine (TAU) contents in adult male rats and to analyze whether chronic hyperprolactinemia may affect these patterns. Rats were turned hyperprolactinemic by a pituitary graft. Plasma prolactin (PRL) levels increased after pituitary grafting at all time points examined. A disruption of the circadian rhythm was observed in pituitary-grafted rats, whereas GABA and TAU content followed daily rhythms in all areas studied in controls. In the mediobasal hypothalamus, two peaks for each amino acid were found at midnight and midday. In the anterior hypothalamus, GABA and TAU showed only one peak of concentration at midnight. In the posterior hypothalamus, the values of both GABA and TAU were higher during the light as compared to the dark phase of the photoperiod. In the median eminence GABA content peaked at 20:00h, the time when TAU exhibited the lowest values. Hyperprolactinemia abolished the 24h changes of GABA in the mediobasal hypothalamus and reduced its content as compared to controls. Hyperprolactinemia advanced the diurnal peak of TAU to 12:00h in the mediobasal hypothalamus and did not modify the 24:00h peak. In the anterior hypothalamus, hyperprolactinemia increased GABA and TAU contents during the light phase while it decreased them during the dark phase of the photoperiod. In the posterior hypothalamus hyperprolactinemia did not modify GABA or TAU patterns as compared to controls. In the median eminence hyperprolactinemia increased the 20:00h peak of GABA and shift advanced the decrease in TAU content at 20:00h and its maximum at 24:00h as compared to controls. These data show that GABA and TAU content exhibit specific daily patterns in each hypothalamic region studied. PRL differentially affects the daily pattern of these amino acids in each hypothalamic region analyzed.     

Ethanol-related changes in substance P in the hypothalamus and anterior pituitary.

The effect of the administration of a rabbit anti-substance P serum (ASPS) was studied in rats receiving an acute injection of ethanol. ASPS lowered serum prolactin levels and reduced the hyperprolactinemia induced by ethanol. ASPS also decreased LH serum levels in both saline- and ethanol-treated rats. The effect of ethanol on the concentration of substance P-like immunoreactivity (SP-LI) in the mediobasal hypothalamus and the anterior pituitary gland was also investigated. Ethanol reduced SP-LI in the mediobasal hypothalamus but increased it in the anterior pituitary gland. The presence of ethanol (50 mM) did not affect the K(+)-evoked release of SP-LI from either mediobasal hypothalamus or anterior pituitary gland, though it increased the SP-LI concentration remaining in this gland. These results indicate that ethanol increases the content of SP-LI in the anterior pituitary gland and suggest that substance P may be involved in the prolactin release induced by the acute administration of ethanol.     

Rates of endogenous noradrenaline release in rat brain, heart and intestines: comparison of results obtained after biosynthesis inhibition and 3H-tyrosine labeling]

After labelling of noradrenaline stores with tyrosine 3H, the rate constant of NA efflux was calculated from the change of the NA-3H and TY-3H specific activities. The biological half-life of NA was 2,2 h in the brain, 24 h in the heart and 3,3 h in the intestine. These values were similar to those obtained after inhibition of NA synthesis by alpha-methylparatyrosine.     

Diurnal variations of medial basal and anterior hypothalamic thyroliberin [TRH] and serum thyrotropin [TSH] concentrations in male rats.

The diurnal variation of TRH concentrations in different parts of hypothalamus was studied in 80 male rats, which were killed in groups of 5 at 3 h intervals. The hypothalamus was dissected into three parts: I) medial basal hypothalamus (MBH), II) anterior hypothalamus, and III) dorsal hypothalamus. Anterior pituitary and serum TSH concentrations were also measured. TRH concentrations were higher in MBH than in the other parts of the hypothalamus: at night 300–450 pg/mg of wet weight of tissue. When the lights were turned on, MBH-TRH levels began to decrease, reaching a nadir of 210 pg/mg at 12 noon. After 15 h, MBH-TRH levels began to increase again. The changes in TRH levels in anterior hypothalamus were usually opposite to those in MBH (r = ?0.6185). Serum TSH levels were about 800 ng/ml during the day and were decreased to about one half of these levels when the lights were turned off. Serum TSH levels were positively correlated with anterior hypothalamic TRH levels (r = 0.6457) and inversely correlated with MBH-TRH levels (r = ?0.7747). Anterior pituitary TSH levels showed small but statistically insignificant variations. In conclusion, there were statistically interrelated diurnal rhythms in anterior hypothalamic and MBH-TRH levels and serum TSH concentrations.     

Adrenalectomy does not affect the nocturnal peak of fos expression within hypothalamic pro-opiomelanocortin neurons

Circulating glucocorticoid (GC) levels are thought to modulate the basal activity of pro-opiomelanocortin (POMC) neurons within the mediobasal hypothalamus (MBH) of the male rat. In a recent study we demonstrated that Fos-immunoreactivity (Fos-IR) was spontaneously induced throughout the dark phase of the light/dark cycle within a large population of these MBH neurons. Here, we have investigated the effect of adrenalectomy on the nocturnal expression of Fos protein within POMC neurons. To this aim, groups of intact (IN), adrenalectomized (ADX) and sham-operated (sham) rats were killed 7 days after surgery (or no surgery) at times when Fos-IR is known to show either nadir (at light offset) or peak (6 h after light offset) values within MBH POMC neurons. Brains were processed for Fos- and/or POMC-immunohistochemistry. The results showed that, at both times studied, 7-day adrenalectomy did not affect the number of POMC/Fos double-stained neurons within the MBH. The rostro-caudal pattern of distribution of such labeled neurons throughout the MBH of ADX rats was also similar to that of IN or sham rats. The present data demonstrate that the nocturnal induction of Fos within MBH POMC neurons is not controlled via the nychtemeral rhythm of secretion of the adrenal gland. Furthermore, this study shows that basal levels of circulating GC do not alter the nocturnal peak of Fos synthesis within POMC neurons.     

Effects of Hypoxia on the Activities of Noradrenergic and Dopaminergic Neurons in the Rat Brain

The effects of hypoxia (10% O2, 90% N2) on the content, biosynthesis, and turnover of noradrenaline (NA) and 3,4-dihydroxyphenylethylamine (dopamine, DA) in the rat brain were examined. Up to 24 h following exposure to hypoxia, NA content in the whole brain was decreased, whereas DA content remained unchanged. The accumulation of 3,4-dihydroxyphenylalanine (DOPA) after central decarboxylase inhibition was decreased. The turnover rate of DA after synthesis inhibition was markedly decreased up to 8 h and returned to the control level within 24 h. In contrast, the turnover rate of NA was all but unchanged, except for a 4-h exposure. The 2-h exposure to the hypoxic environment resulted in a significant decrease in NA content and DOPA accumulation in all brain regions tested, but no significant change was observed in DA content. The turnover rate of DA was remarkably decreased in all brain regions tested, whereas the rate of NA was slightly decreased only in the cerebral cortex and hippocampus. These results suggest that although hypoxia decreases the biosynthesis of both NA and DA, the effects of oxygen depletion on the functional activities of NA neurons differ considerably from those of DA neurons: Only in the cerebral cortex and hippocampus are the NA neurons slightly sensitive to hypoxia, whereas the DA neurons are most sensitive in all brain regions.     

Changes in estrogen receptors in the mediobasal hypothalamus mediate the facilitory effects exerted by the male's olfactory cues and progesterone on feminine behavior in the male rat

The purpose of this study was to determine whether facilitory effects exerted by olfactory cues on lordosis behavior in the male rat involved changes in estradiol receptors at the hypothalamic level. Male rats were orchidectomized as adults. They were given either 25 micrograms estradiol benzoate (EB) alone or 25 micrograms EB and 100 micrograms progesterone (P) sequentially and exposed or not to the odor of male urine. Some of them were tested for lordosis behavior at 8 h after P. The other ones were killed 4 h after P and used for estradiol (E2) and P receptor assay in mediobasal hypothalamus (MBH). Olfactory cues were shown to increase the number of E2 receptors in both the animals given EB or EB + P. Progesterone as such appeared to be capable of increasing the number and the rate of occupancy of E2 receptors. A population of constitutive and estrogen-inducible P receptors was detected in the MBH. Since only the animals given EB + P were shown to be sensible to the facilitory effects of male urine on lordosis behavior, it may be assumed that E2 and P on one hand and olfactory cues on the other exert cumulative effects at the level of the MBH and that both a high level and a high rate of occupancy of E2 receptors are necessary for the olfactory cues to facilitate the display of lordosis behavior in the male rat.     

Time Course of the Metabolite Patterns of Intraventricularly Injected [3H]Noradrenaline in Rat Brain Regions

In the hypothalamus, septum, pons with medulla, and hippocampus regions of rat brain, the level of radioactivity of [3H]noradrenaline and of five of its metabolites were determined up to 6 h after intraventricular injection of the tritiated amine. The following main results were found: In anterior hypothalamus and septum, the [3H]noradrenaline level declined in two phases. Similar turnover curves were obtained for the primary deaminated metabolites, with almost the same final half-lives as for [3H]noradrenaline. The level of the initial methylation product, normetanephrine, also showed a biphasic decline, which did not correspond to that of [3H]noradrenaline but rather was faster throughout the experiment. The final metabolites (i.e., the glycol sulfates) reached maximal levels in hypothalamus and septum earlier than in other regions. Thereafter, their levels declined with almost similar rates in all areas tested, but always faster than the [3H]noradrenaline level. The following conclusions were drawn: In areas rich in catecholaminergic nerve terminals, there seems to be a site, in addition to the vesicular storage pool, that accumulates exogenous noradrenaline and then releases it with relatively short half-lives. The contents of primary deaminated metabolites followed the turnover of [3H]noradrenaline at both sites. Exogenous [3H]noradrenaline seems to be methylated at two extraneuronal sites, which are distinguished by the rates of subsequent deamination. The size of the pool of slowly deaminated [3H]normetanephrine that is formed immediately after [3H]noradrenaline injection determined the apparent turnover of this product throughout the experiment and, thus, like the final metabolites, reflects for several hours the initial degradation of the unstored [3H]noradrenaline, rather than the metabolism of the stored amine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cadmium effects on hypothalamic-pituitary-testicular axis in male rats

This study analyzes cadmium effects at the hypothalamic-pituitary-testicular axis. Male rats were given cadmium during puberty or adulthood. Cadmium exposure through puberty increased norepinephrine content in all hypothalamic areas studied, but not in the median eminence. Metal exposure increased serotonin turnover in median eminence and the anterior hypothalamus, while decreased it in mediobasal hypothalamus. Also, decreased plasma levels of testosterone were found. Cadmium exposure during adulthood increased norepinephrine content in posterior hypothalamus and decreased the neuro-transmitter content in anterior and mediobasal hypothalamus. Decreased circulating levels of luteinizing hormone (LH) and testosterone and increased plasma follicle stimulating hormone (FSH) levels were also observed. Cadmium accumulated in all analyzed tissues. Various parameters showed age-dependent changes. These data suggest that cadmium globally effects hypothalamic-pituitary-testicular axis function by acting at the three levels analyzed and that an interaction between cadmium exposure and age emerge.     

Effects of a major androgen-dependent urinary protein, alpha 2u-globulin on the pituitary-gonadal axis and hypothalamic monoamines in adult male mice.

The purpose of the present study was to evaluate the effects of alpha-2u-globulin, a sex-dependent male rat urinary protein on pituitary-gonadal functions and hypothalamic monoamine contents in male mice. Adult male mice, maintained under standardized laboratory conditions (L:D, 14:10) were injected subcutaneously with alpha-2u-globulin at a dose of 1 mg/animal/day or with vehicle daily for 14 days and killed 16 h after the last injection. Plasma levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T) and testicular levels of T were measured by radioimmunoassays. The concentrations of norepinephrine (NE), dopamine (DA) and serotonin (5-HT) in medial basal hypothalamus (MBH) and anterior hypothalamus (AH) were measured by high performance liquid chromatography. Administration of alpha-2u-globulin led to a significant increase in plasma FSH and LH levels (P less than 0.05) as well as in plasma and testicular T levels (P less than 0.025). In the MBH of alpha-2u-globulin treated mice, there were significant elevations of NE (P less than 0.025), DA (P less than 0.01) and 5-HT (P less than 0.025) contents. In the AH, both DA (P less than 0.025) and 5-HT (P less than 0.01) contents were decreased while NE content remained unaltered. These results indicate that administration of alpha-2u-globulin can lead to a significant stimulation of pituitary-testicular axis and that this effect may be mediated through alteration of hypothalamic monoamines.     

Norepinephrine Turnover in the Hypothalamus of Adult Male Rats: Alteration of Circadian Patterns by Semistarvation

Norepinephrine (NE) turnover, as estimated by 3-methoxy-4-hydroxyphenylethyleneglycol concentration, was studied in the mediobasal hypothalamus of control and semistarved adult male rats at eight time points of a 24-h period. The marked circadian periodicity of NE turnover with a peak in the dark phase in control rats is completely suppressed in semistarved rats. The average 24-h concentration of the NE precursor tyrosine in brain and of tyrosine flow into brain (calculated from plasma amino acid concentrations) is reduced in semistarved rats, but both brain tyrosine and tyrosine flow show continuing circadian fluctuations.     

Effect of alcohol on the content of sex steroid receptors in the hypothalamus and hypophysis of male rats

In experimental dipsomania model (formation of physical dependence by method of intensive alcoholization) we have studied receptor binding of testosterone (T) and estradiol (E2) in the hypothalamus and pituitary body of mature male rats. Administration (at 10 and 16 h) of 25% ethanol-saline solution at a dose of 7.5 g/kg of body weight in the course of 5 days significantly decreased serum T level but did not change serum LH and FSH levels. Essential reduction of the nuclear androgen receptors in the preoptic-anterior hypothalamic area (POA), mediobasal hypothalamus (MBH) and adenohypophysis was noted in alcohol-treated rats. Unlike androgen receptors the number of the nuclear E2-binding sites in PaO was significantly increased in these males. Thus the results of the present paper demonstrate that multiple administration of ethanol stipulates deficit of serum T, androgen receptors in MBH and pituitary body that possibly results in separation of negative feedback mechanism between the gonads and pituitary body. Increase of specific binding of E2 to nuclear receptors in PoA might appear to explain feminization of alcohol-treated rats.