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Journal Article 2010; 31(3): 359-362 PubMed PMID: 20588235 Citation  Keywords:  Adult, Dopamine:physiology, Female, Genetic Predisposition to Disease, Haloperidol:pharmacology, Humans, Huntingtin Protein, Huntington Disease:blood, Hypothalamo-Hypophyseal System:drug effects, Male, Middle Aged, Nerve Tissue Proteins:genetics, Nuclear .   

OBJECTIVES: In addition to neuronal loss in striatum and cerebral cortex that characterizes Huntington's disease (HD), hypothalamic atrophy has also been found only in certain areas, probably not including dopaminergic functions.

METHODS: We assessed the reactivity of the hypothalamus-pituitary dopaminergic system by measuring the acute prolactin (PRL) responses to 5 mg i.m. haloperidol in male and female HD patients and in female subjects with expanded CAG repeats in the Huntington gene before disease onset, as well as in a group of healthy males.

RESULTS: The responses of the male patients were similar to those of a group of male healthy volunteers. Females gave higher PRL responses, with no differences in the response patterns of female patients and females at risk for HD. PRL elevations were not related to severity of illness, or to presence of dementia, depression, or psychotic features.

CONCLUSIONS: The results implicate a normal dopaminergic input from hypothalamus to pituitary and preserved pituitary dopamine receptors, indicating that hypothalamic atrophy in HD does not affect mechanisms involved in PRL secretion by haloperidol....

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Evaluation Studies 2009; 30(1): 11-16 PubMed PMID: 19300389 Citation  Keywords:  Antidepressive Agents:pharmacology, Humans, Hypothalamo-Hypophyseal System:drug effects, Mood Disorders:drug therapy, Pituitary-Adrenal System:drug effects, Receptors, Glucocorticoid:physiology, Transcription, Genetic:physiology,.   

: Changes in the hypothalamic-pituitary-adrenal (HPA) axis are characteristic of major depression. Because the effects of glucocorticoids are mediated by intracellular receptors including, most notably, the glucocorticoid receptor (GR), several studies have examined the number and/or function of GR's in depressed patients. Review scientific evidences have consistently demonstrated that GR function is impaired in major depression, resulting in reduced GR-mediated negative feedback on the HPA axis and increased production and secretion of corticotropin-releasing hormone (CRH) in various brain regions postulated to be involved in the causality of major depression. Hyperactivity of HPA axis is the main biochemical change, besides disturbed monoaminergic neurotransmission, observed in the patients suffering from a major depression. High incidence of depression in Cushing's syndrome as well as antidepressant effects of adrenocortical enzyme inhibitors in major depression support hypothesis that hyperactivity of HPA axis may be involved in pathogenesis of depression. Major alterations of the HPA axis that can be reversed by successful antidepressant therapy are often seen in depressed patients. A possible explanation for this is that the antidepressant-induced increase in GR's renders the HPA axis more sensitive to glucocorticoid feedback. This new insight into antidepressant drug action suggests a novel approach to the development of antidepressant drugs....

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Comparative Study 2007; 28(5): 614-620 PubMed PMID: 17984940 Citation  Keywords:  Adrenal Medulla:drug effects, Adrenergic Uptake Inhibitors:pharmacology, Adrenocorticotropic Hormone:blood, Analysis of Variance, Animals, Corticosterone:blood, Epinephrine:blood, Fluoxetine:pharmacology, Hypothalamo-Hypophyseal System:drug effects, Male,.   

OBJECTIVE: To estimate the influence of long-term treatment with noradrenergic and serotonergic reuptake inhibitors on activity of pituitary-adrenocortical and sympatho-adrenomedullar systems in animals, we compared the effects of maprotiline (a selective inhibitor of noradrenaline reuptake) and fluxilan (a selective inhibitor of serotonin reuptake) on plasma noradrenaline (NA), adrenaline (A), adrenocorticotropic hormone (ACTH) and corticosterone (CORT) levels in unstressed control and rats exposed to chronic unpredictable mild stress (CUMS).

METHODS: Plasma NA and A were assayed by a radioenzymatic method. Plasma CORT was measured using RIA kits and plasma ACTH by a chemiluminescent method.

RESULTS: CUMS did not affect blood plasma NA, A and ACTH content, but elevated plasma CORT level. Maprotiline elevated plasma NA content both in unstressed control and CUMS group, whereas plasma A remained unchanged. Fluxilan acted significantly increasing plasma NA and A concentrations both in control and CUMS rats. Neither maprotiline nor fluxilan affected plasma ACTH level both in unstressed control and CUMS animals. Plasma CORT level in unstressed control rats remained unchanged after maprotiline and fluxilan treatment, while being significantly decreased in CUMS rats.

CONCLUSION: Chronic treatment of adult rat males with maprotiline, a noradrenaline reuptake inhibitor activated sympathoneural system. On the other hand, fluxilan, a serotonin reuptake inhibitor activated both sympathoneural and adrenomedullar system, whereas both antidepressants desensitized HPA axis. The findings described here suggest that elevated plasma catecholamines my contribute to adverse effects of these drugs on cardiovascular parameters during antidepressant therapy....

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Clinical Trial 2006; 27(3): 355-358 PubMed PMID: 16816832 Citation  Keywords:  Aged, Amyotrophic Lateral Sclerosis:drug therapy, Analysis of Variance, Dopamine:metabolism, Erythropoietin:metabolism, Female, Humans, Hypothalamo-Hypophyseal System:drug effects, Injections, Intravenous, Male, Middle Aged, Neuroprotective Agents:metabol.   

OBJECTIVES: The presence of erythropoietin (EPO) and its receptors in several central nervous system regions indicates additional functions beside its hematopoietic role. Preclinical data suggest that it may slow down the process of neuronal loss, and that EPO may cause dopamine release, and thus influence hormone release, especially prolactin. This possibility has not yet been studied in humans.

METHODS: During a clinical trial on possible protective effects in patients with amyotrophic lateral sclerosis (ALS), we studied the acute effects of EPO administration on prolactin, the release of which is under tonic inhibition of hypothalamic-pituitary dopaminergic activity. Prolactin as well as EPO levels were estimated in blood samples taken every 30 min over 2 hours after administration of 3000 IU EPO i.v. in seven male and four female patients with ALS.

RESULTS: The baseline PRL levels of the 11 patients were all within normal range (4.5-10.5 ng/ml). EPO administration caused a significant reduction in prolactin levels, maximal at 60 min after administration. Reductions in PRL were not related to EPO dose (IU per kg body weight), or to duration of illness.

CONCLUSIONS: The findings indicate that EPO promotes dopamine release in humans, and is consistent with preclinical data showing that EPO releases dopamine from rat striatal slices. Previous reports showed that dopaminergic neurons express EPO receptors, which exert a facilitating action on dopamine release, and the present data indicate that this may hold true in humans....

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Comment 2005; 26(6): 757-758 PubMed PMID: 16380670 Citation  Keywords:  Circadian Rhythm:drug effects, Diabetes Mellitus, Type 2:blood, Double-Blind Method, Humans, Hydrocortisone:blood, Hypoglycemic Agents:pharmacology, Hypothalamo-Hypophyseal System:drug effects, PPAR gamma:agonists, Pituitary-Adrenal System:drug effects, T.   

OBJECTIVES: PPAR-gamma agonists are able to inhibit pituitary tumour development and tumoral hormonal secretion in rodents both in vitro and in vivo. Their use for treatment of Cushing Disease (CD) has been suggested but the clinical experience with the two PPAR-gamma agonists commercially available (rosiglitazone and pioglitazone) was not impressive. Short-time treatment has been proposed to be the cause of unsuccessful results on CD in humans. We report here the effect on early-morning plasma cortisol levels of a long-time treatment with rosiglitazone at the highest approved dose.

METHODS: Because PPAR-gamma receptors are located in normal corticotroph cells we tested in a placebo-controlled study the influence of rosiglitazone on cortisol secretion. The study enrolled 30 newly diagnosed type 2 patients which were assigned to receive either rosiglitazone (8 mg/day) or placebo. Plasma morning cortisol (8.00 a.m.) was measured at the baseline and at the end of the study.

RESULTS: Rosiglitazone vs placebo did not modify the early morning plasma levels of cortisol (13 microg/dl [3-21] vs 11 microg/dl [7-23] [median and range]) after 26 weeks of treatment.

CONCLUSION: The discrepancy between in vitro and animal data on one side and clinical data on the other side warrant further investigations into the mechanisms of action of PPAR-gamma agonists on ACTH secretion before other clinical studies will be conducted....

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Clinical Trial 2004; 25(6): 438-442 PubMed PMID: 15665807 Citation  Keywords:  Adult, Estradiol:blood, Follicle Stimulating Hormone:blood, Humans, Hypothalamo-Hypophyseal System:drug effects, Klinefelter Syndrome:blood, Luteinizing Hormone:blood, Male, Naloxone:administration & dosage, Narcotic Antagonists:administration & dosage, P.   

UNLABELLED: AIM TO THE STUDY: The investigation of the influence of anti-opioid drug on hypophyseal and gonadal hormones secretion in case of Klinefelter syndrome.

MATERIAL AND METHODS: The naloxone test (0,4 mg iv) was performed in 14 patients with Klinefelter syndrome aged from 19 to 32 and in 12 age matched control subjects with azoospermia and normal spermatogenesis in testicular histology. The plasma levels of FSH, LH, prolactin, testosterone and estradiol were established before and after 30, 60, 60 and 120 minutes respectively, following the drug administration.

RESULTS: Basal FSH, prolactin and estradiol levels were significantly higher whereas basal testosterone was significantly lower in patients with Klinefelter syndrome than in the control group. After the naloxone administration the mean plasma prolactin level decreased significantly (p=0.01) in Klinefelter subjects. The respective diminution in control group was not significant. The levels of FSH and LH as well as testosterone and estradiol did not change during the naloxone test in both Klinefelter and control subjects.

CONCLUSIONS: The naloxone administration in Klinefelter syndrome caused the decrease in plasma prolactin levels but did not affect the plasma level of another hypophyseal and gonadal hormones. The opioid controlled gonadotropin secretion is altered in case of Klinefelter syndrome....

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Clinical Trial 2004; 25(1-2): 135-140 PubMed PMID: 15159697 Citation  Keywords:  Adult, Analysis of Variance, Antipsychotic Agents:pharmacology, Benzodiazepines:pharmacology, Dibenzothiazepines:pharmacology, Gonadal Steroid Hormones:blood, Humans, Hypothalamo-Hypophyseal System:drug effects, Indoles:pharmacology, Isoindoles, Male, Pit.   

OBJECTIVES: We investigated the effects of a switch from typical to atypical antipsychotic drugs (olanzapine, n=8; perospirone, n=9; or quetiapine, n=13) on quality of life and hypothalamo-pituitary-gonadal axis hormones.

METHODS: The subjects were 30 male chronic schizophrenia inpatients. The assessment was done before and after the switch.

RESULTS: After the switch, (i) scores of the Brief Psychiatric Rating Scale total and three factors (anxiety-depression, anergia, and thought disturbance) decreased, (ii) the overall severity score of the Drug Induced Extra-Pyramidal Symptoms Scale tended to decrease, (iii) prolactin decreased but gonadal hormones remained unchanged, and (iv) scores on all three subscales (psychosocial, motivation/energy, and symptoms/side effects) in the Japanese version of the Schizophrenia Quality of Life Scale (JSQLS) decreased. However, there were no significant group effects, or time-by-group interactions. In addition, score changes from baseline in psychosocial and motivation/energy subscales in the JSQLS were correlated with those in psychotic symptoms, particularly in the anxiety-depression factor. Moreover, responders had been taking lower doses of typical antipsychotic drugs, and had higher serum estradiol concentrations than non-responders before the switch.

CONCLUSIONS: The study indicated that the switch to atypical antipsychotic drugs was effective in reducing elevated prolactin without affecting the gonadal hormones and in improving quality of life patients who had been treated with typical antipsychotic drugs....

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Journal Article 2001; 22(4): 243-247 PubMed PMID: 11524630 Citation  Keywords:  Adult, Anti-Anxiety Agents:therapeutic use, Anxiety Disorders:drug therapy, Genitalia, Male:drug effects, Gonadotropins:blood, Humans, Hypothalamo-Hypophyseal System:drug effects, Isoindoles, Male, Middle Aged, Piperazines:therapeutic use, Prolactin:blood.   

BACKGROUND: Serotonin (5-HT) agonists are reported to affect prolactin (PRL) and gonadotropin secretion. A small study was conducted on male patients with generalized anxiety disorders to investigate the clinical and neuroendocrinological effects of the 5-HT(1A) receptor agonist tandospirone (TDS) on the hypothalamo-pituitary-gonadal (HPG) axis.

METHODS: The subjects for the present study included 11 male outpatients. Informed consent was obtained from all subjects involved in this study. The endocrine studies were done before and during TDS administration. Psychiatric ratings were done using the Japanese version of the Spielberger's State-Trait Anxiety Inventory.

RESULTS: We found that both state- and trait-anxiety scores were significantly reduced by TDS treatment; there was no significant difference in PRL, gonadotropins or testosterone (T) between the patients and normal controls; TDS administration showed significant stimulatory effects on PRL and T; and PRL change between baseline and TDS steady state (DeltaPRL) did not show a significant correlation with improvement in state or trait-anxiety scores.

CONCLUSIONS: Our results indicate that PRL response may not provide a clinical predictor; (2) PRL level may not reflect the level of anxiety, and 5-HT(1A) may have stimulatory effects on PRL. However, further, double-blind evaluation with a larger sample would be needed for clarification of effects of 5-HT(1A) on the HPG axis....

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