Correlation between the pineal and brain 5-hydroxytryptamine rhythms and adrenal functions in male rats.
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Biomedical subjects
Publications and source records attributed to G Telegdy.
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The effects of androgenic steroids on the dopamine (DA), noradrenaline (NA) and 5-hydroxytryptamine (5-HT) contents of different brain regions have been studied in order to elucidate the possible involvement of neurotransmitters in the negative feedback action of androgens. Administration of testosterone propionate (TP); (100 micrograms/kg or 5 mg/kg, i.p.) increased plasma testosterones, which reached a maximum at about 30 min following injections. TP (100 micrograms/kg) decreased the DA level in the hypothalamus to a minimum after 30 min and returned to normal level after 120 min. There was no effect in the amygdala, striatum and mesencephalon. Subsequent to 5 mg/kg i.p. TP administration, the minimum in the DA level was observed between 90 and 120 min in the hypothalamus, and after 120 min in the amygdala, but the treatment was without effect in the striatum and mesencephalon. Both doses of TP were ineffective as regards for in altering NA and 5-HT levels in the brain areas studied. In a dose of 5 mg/kg, androgens of different activities, such as norandrostenolone, dihydrostestosterone and androstenedione, decreased the DA contents of the hypothalamus and amygdala regions, but pregnenolone was ineffective. None of the androgens affected the NA and 5-HT levels in the brain areas studied. The data suggest that some of the actions of androgens are mediated via a dopaminergic mechanism in which not only the hypothalamus but also the amygdala is involved.
The effects of different drugs influencing brain neurotransmitter contents have been tested on the pituitary-testicular function in male rats. L-dopa (200 mg/kg body weight, i.p.) increased the dopamine and noradrenaline contents of the hypothalamus, amygdala, striatum and mesencephalon, but it was ineffective as regards the 5-hydroxytryptamine contents of the same brain areas, and increased the plasma testosterone level. alpha-Methyl-p-tyrosine (250 mg/kg b.w., i.p.) decreased the dopamine and noradrenaline contents of these brain areas, but it was ineffective to 5-hydroxytryptamine, and decreased the plasma testosterone level. Diethyldithiocarbamate (400 mg/kg b.w., i.p. twice a day) increased the dopamine levels in the hypothalamus, amygdala, striatum and mesencephalon, decreased the noradrenaline contents in the same brain regions but had no effect on the 5-hydroxytryptamine contents of these brain areas or on the testosterone level in the peripheral blood. p-Chlorophenylalanine (300 mg/kg b.w., i.p.) decreased the 5-hydroxytryptamine contents of the different brain areas, while it had no effect on the dopamine and noradrenaline levels or on the plasma testosterone level. 5-Hydroxytryptophan (200 mg/kg b.w., i.p.) increased the 5-hydroxytryptamine contents of all brain areas studied, but was without effect on the dopamine and noradrenaline contents or the plasma testosterone level. The data suggest that both dopamine and noradrenaline may be involved in the regulation of the pituitary-testicular function, and the ratio of the two transmitters might be more important that their actual levels in definite brain areas.
The effects of different neurotransmitters were tested in vitro on a hypothalamic tissue, collagenase-digested isolated anterior pituitary and Leydig cell suspension system by measuring the testosterone production of the Leydig cells. Neurotransmitters were used in concentrations of 0.25, 1.0, 2.5, 5.0, and 10.0 micrograms/ml incubation medium. Dopamine in doses of 1.0, 2.5, and 5.0 micrograms/ml increased the hypothalamic tissue-induced pituitary-testis activation, while it had no direct effect on pituitary and Leydig cells. Noradrenaline in the concentration range 2.5--10.0 micrograms/ml decreased the luteinizing-hormone-releasing-hormone (LHRH) sensitivity of the pituitary cells. 5.0 and 10.0 micrograms/ml 5-hydroxytryptamine decreased the testosterone production and the hCG sensitivity of the isolated Leydig cells. Carbamylcholine and pilocarpine had no action on the in vitro system at the different levels studied.
The level of protease acrosin in the seminal plasma of oligozoospermic men was significantly higher than that of normozoospermic men. The amount of bradykininase in the seminal plasma was very high in both normozoospermic and oligozoospermic patients. When the acrosin and kininase content was referred to one million spermatozoa, seminal plasma kininase was significantly enhanced in oligozoospermic men, while the acrosin activity was similar in normozoospermic fertile men and infertile men. Human seminal plasma inhibitor I (HUSI I) increased along with sperm count. Human seminal plasma inhibitor II (HUSI II) showed no change. The motility of spermatozoa was depressed in oligozoospermic patients.
An in vitro system consisting of the rat hypothalamic tissue, the collagenase-digested isolated anterior pituitary cells and the Leydig cells, has been employed, where the testosterone production of the incubated Leydig cells was measured as the end point. The method appeared to be highly sensitive and specific in studying the functional interrelations of hypothalamus-pituitary-testis system. The sensitivity of the Leydig cells to hCG was 0.1--1.0 mU per 10(6) cells, and that of the anterior pituitary cells to LHRH responding with LH release was in the range of 0.1--1.0 ng per 10(6) cells. Two hypothalamic blocks can release a sufficient amount of LHRH to produce LH secretion in the pituitary cell preparation. The described technique seems to be a suitable in vitro approach for measuring the functional activity of the system studied and for evaluation of the sites of response to various external agents.
The effect of prostaglandins (PG) A1, E1, E2 and F2 alpha in the concentration range of 10(-7)--10(-4) M were studied in vitro on a rat hypothalamic tissue, collagenase-digested isolated anterior pituitary cell and Leydig cell suspension system by measuring the testosterone production of incubated Leydig cells. PGs did not change the testosterone production and the hCG sensitivity of the Leydig cells, nor the LH secretion and the LHRH sensitivity of the anterior pituitary cells. PGE2 at concentrations of 10(-6), 10(-5) and 10(-4) M significantly increased the hypothalamic tissue-induced pituitary-testicular activation, and this stimulatory effect of PGE2 was dose dependent. PGA1, PGE1 and PGF2 alpha did not alter hypothalamic LHRH release measured in vitro. The results suggest that PGE2 has a direct stimulatory effect on hypothalamic LHRH release.
The effect of adrenal and gonadal hormones on vascular permeability induced by intradermal injection of prostaglandins (PGs) E1, F2alfa, arachidonic acid and compound 48/80 have been examined in the rate. PGE1, arachidonic acid and compound 48/80 produced an increase in local vascular permeability. PGF2alfa decreased the action of these vasoactive agents, when it was injected in a mixture intradermally with PGE1, arachidonic acid and compound 48/80. Vasoactive response induced by PGE1, arachidonic acid and compound 48/80 was inhibited by the removal of adrenals and testes, and it was restored to normal by injection either of cortisol, deoxycorticosterone (DOC) or testosterone. In adrenalectomized rats, no change was observed in the inhibition of vascular permeability elicited by PGF2alfa response to compound 48/80. The blocking effect of PGF2alfa on vascular permeability evoked by PGE1 and arachidonic acid showed a considerable decrease. After orchidectomy the inhibitory effect of PGF2alfa on the vascular permeability induced by arachidonic acid and compound 48/80 was completely blocked, while in the case of PGE1 the inhibition was partial. Testosterone treatment restored the anti-inflammatory effect of PGF2alfa against compound 48/80. Ovariectomy was without any effect on vascular response.
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Fifteen min after ether stress, the 5-hydroxytryptamine (5-HT) content of the rat hypothalamus decreased, while after electric shock no decline was noted in the mesencephalon and the hypothalamus. At 30 min an increase occurred in the mesencephalon and amygdala and at 60 min in the hypothalamus after both stressors. Fifteen min after electric shock the 5-hydroxyindoleacetic acid (5-HIAA) content was increased in the amygdala, while after both stressors in the mesencephalon and hypothalamus 30 min and after ether stress in the amygdala. In the hippocampus and the septum the 5-HT or 5-HIIA content was unaffected by either type of stress. 5-HT turnover decreased between 10 and 20 min after ether stress in the hypothalamus and after electric shock in the mesencephalon and hypothalamus. Between 50 and 60 min after electric shock, 5-HT turnover increased in the mesencephalon. Other brain areas showed no significant difference from the control 5-HT value. 3H-5-HT uptake decreased in the mesencephalon and hypothalamus 20 min after ether stress, but returned to normal after 60 min. The plasma corticosterone level was highest at 30 min after both stressors and returned to normal 90 min after stress. Therefore, the stress-induced decrease of serotoninergic activity in certain limbic brain structures, especially in the hypothalamus, suggests an inverse relationship with pituitary-adrenal activity. This finding would further support the concept that the serotoninergic system plays an inhibitory role in pituitary-adrenal function.
Performance of an active avoidance (bench-jumping) reflex has been studied in rats during stimulation of the midbrain raphe nuclei. Raphe stimulation (10 cps, 0.2 msec, 2.5-5.0 V) inhibited the performance of the reflex. A serotonin receptor blocker (methysergide, 2.0 mg/kg IP) increased the reflex performance in non-stimulated animals and prevented the action of raphe stimulation. The data indicate that the cerebral serotoninergic system might have an inhibitory control over the performance of conditioned avoidance reflex.
Oxytocin (500 mu u) and vasopressin (50 mu u) were injected into the lateral ventricle and its effect on hypothalamic self-stimulation has been studied. Oxytocin increased, while vasopressin decreased the self-stimulation rate tested 10-20 min following application. The hypothalamic and mesencephalic serotonin content decreased slightly while plasma corticosterone content did not change 20 min after oxytocin and vasopressin administration compared to the injected control animals. The data suggest that vasopressin and oxytocin have an opposite effect on self-stimulation and this action is not mediated through the brain serotoninergic or pituitary-adrenocortical axis.
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