精神分裂症患者血清催乳素和生长激素水平的观察

为研究精神分裂症患者血清中催乳素（ＰＲＬ）、生长激素（ＧＨ）的基础水平与正常人的差异，及精神分裂症患者治疗前后ＰＲＬ、ＧＨ水平的变化，以及与临床疗效的关系，采用放射免疫法，测定２０例精神分裂症患者治疗前和治疗后第２，４，６，８周末的ＰＲＬ、ＧＨ水平，并与１０名正常人对照，同时进行治疗前和治疗后第２，４，８周末简明精神病评定量表（ＢＰＲＳ）的评定。结果显示：精神分裂症患者的基础ＰＲＬ水平较正常对照组低，而ＧＨ水平较高，但无统计学意义；用抗精神病药治疗后ＰＲＬ升高，ＧＨ下降，ＰＲＬ水平的升高与ＢＰＲＳ减分值明显相关，支持精神分裂症的多巴胺功能亢进的假说。提示ＰＲＬ对治疗的反应可能是预测临床疗效的一个指标。     

Thyroid hormones and TSH, prolactin and LH responses to repeated TRH and LRH injections in depressed patients.

Twelve patients with unipolar depressive disorders received 600 microgram of synthetic TRH or LRH, in a random order, for 3 days each. Placebo injections were given as two 3-day courses prior to and between the active treatments. Serum TSH, prolactin (Prl) and LH were measured by radioimmunoassays prior to the experiment as well as immediately before and 20 min after each injection. Serum T4 and T3 were determined by radioimmunoassays before the treatments and 24 h after the first two TRH injections. Serum T4 level in depressed patients did not differ from controls. Serum T3 level in depressed patients was significantly below, and the reverse T3 level was slightly above the normal mean. However, the latter difference was not statistically significant due to the large variation of rT3 levels among the depressed patients. The TSH responses did not differ from that of controls after the first injection but the responses after the second injection were lower than in a control study. The Prl responses to TRH were sub-normal in seven out of eight patients. Blunted LH responses to LRH were seen in three patients.     

Differential prolactin responses to Haloperidol and TRH in normal adult men

(1) Prolactin (PRL) responses to low dose intravenous (i.v.) haloperidol differed among individuals, but PRL responses to 25 μg and 500 μg i.v. thyrotropin-releasing hormone (TRH) in the same subjects were similar. (2) Serum concentrations of haloperidol accounted for only 36% of the variability in PRL response. (3) It is concluded that the inter-individual variability in PRL response to haloperidol does not result from differences in pituitary PRL-secreting capacity, nor can it be attributed in a major way to differences in drug metabolism. It is proposed that the variable PRL responses to haloperidol reflect individual differences in dopamine receptor sensitivity to blockade by this drug.     

TRH tests with analyses of TSH, prolactin, and GH responses in subtypes of patients with major depressive disorders

TRH tests were performed on 131 patients with RDC diagnoses of major depressive disorders to study altered endocrine control mechanisms in subtypes of depression. The TSH response to TRH was measured in all patients. In more than a third of the sample the prolactin (PRL) and growth hormone (GH) responses were also analysed. There were no differences between bipolar, primary unipolar and secondary unipolar patients in means of any endocrine variable. However, the expected positive correlation between baseline TSH and delta TSH was absent in the secondary unipolar group, indicating a dysregulation of pituitary TRH receptor sensitivity in this depressive subtype. Only delta TSH was dependent on depressive state, being lower in currently ill primary unipolar patients only. Patients with melancholic features (endogeneity scores high) had blunted TSH responses. Weight loss was connected with TSH blunting in all depressive subtypes. Among patients with blunted delta TSH (less than 5 mU/l) there was no relationship between degree of weight loss and delta TSH. Further, examination of partial correlation coefficients suggests weight loss of affect delta TSH by virtue of its being part of the melancholic syndrome. A significant correlation between blunted delta TSH and nonsuppression of cortisol in the DST was found only among primary unipolar patients, arguing for some independence of the TRH test and the DST in mirroring disturbed endocrine controls in depression.     

Delayed TSH release in anorexia nervosa following injection of thyrotropin-releasing hormone (TRH)

We studied plasma concentrations of thyrotropin (TSH), prolactin and growth hormone (GH) after injection of 500 microgram of thyrotropin-releasing hormone (TRH) in 10 patients with acute anorexia nervosa, subsequent to initial nutritional stabilization and again after weight recovery. Plasma thyroxine levels were normal throughout, whereas plasma triiodothyronine levels were low initially but rose with weight gain. The TSH secretory response to TRH was delayed and prolonged during the initial study but showed a normal overall quantitative response, except for two patients who showed no TSH rise. Following weight gain the TSH response was more rapid, and positive correlations were found between body weight and peak TSH levels and rapidity of TSH response. Six of 10 patients, however, continued to exhibit a delayed TSH peak response, the average response was markedly increased in comparison with that in normal females. The prolactin response curves were normal at both times. Rises in GH following TRH were observed in two patients prior to and in one patient after weight gain. We conclude that acute anorexia nervosa, with its concomitant profound weight loss, is accompanied by abnormalities in the hypothalamo-pituitary-thyroid axis, which are reversed only in part with improvement in the illness and weight gain, suggesting the persistence of disordered neuroendocrine function in this illness.     

Plasma profiles of adrenocorticotropic hormone,cortisol, growth hormone and prolactin in patients with untreated parkinson's disease

Summary Plasma profiles of prolactin, growth hormone, adrenocorticotropic hormone (ACTH) and cortisol were evaluated in a group of untreated patients with idiopathic Parkinson's disease and a group of healthy age-matched controls. Plasma integrated concentrations of all hormones except prolactin were significantly lower in the patients as compared with the controls; however, prolactin nocturnal peak concentration was significantly elevated in the patients; nocturnal growth hormone levels were significantly reduced in the Parkinson group; ACTH and cortisol plasma concentrations were also consistently lower during most of the day in the patients with Parkinson's disease. These data confirm the presence of a hypothalamic disturbance in patients with idopathic Parkinson's disease, which can affect pituitary function.     

Blunted TSH response to TRH and seizure duration in ECT

The relationship between the thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH) and the duration of seizures induced by electroconvulsive therapy (ECT) in depressed patients was investigated. In a balanced-order cross-over design, 16 depressed women were given 0.4 mg TRH or placebo intravenously, 20 min before ECT in the first two sessions. In the third ECT session TRH was given just prior to ECT. Thyrotropin (TSH) levels at various sampling times, as well as the duration of seizures, were measured. There was a significant inverse correlation between plasma TSH concentrations 20 min after TRH administration (deltaTSH) and seizure duration. Furthermore, when patients were categorized according to their TSH response to TRH, the group with blunted responses (deltaTSH <6 microIU/ mL, n = 7) had a longer seizure time during ECT than the group with non-blunted responses (deltaTSH > 6 microIU/mL, n = 9). Finally, the seizure duration in the group with blunted TSH responses was reduced significantly when TRH was co-administered, while it remained unchanged in the group with non-blunted TSH responses. It is concluded that a blunted TSH response to TRH might indicate a seizure susceptibility as measured by the duration of seizures induced by ECT. The fact that TRH pre-administration had a reducing effect suggests that this substance might be involved in the pathophysiology of ECT-induced seizures.     

Orphanin FQ stimulates prolactin and growth hormone release in male and female rats

Intracerebroventricular administration of Orphanin FQ (5.5, 55 or 550 pmol) caused a dose-related increase in prolactin secretion in both male and female rats and stimulated GH secretion in males. The magnitude of the prolactin secretory response was greater in females than in males. These effects of OFQ on prolactin and growth hormone release are the same as the stimulatory effects of the endogenous opioid peptides.     

Dexamethasone suppression test, TRH test and Newcastle II depression rating in the diagnosis of depressive disorders

The dexamethasone suppression test (DST), the thyrotropin releasing hormone (TRH) test and the Newcastle II depression rating (NII) were compared with the clinical diagnosis and evaluated in 61 patients fulfilling the criteria of an affective disorder according to the DSM-III classification. A statistically significant correlation between clinical diagnosis and DST as well as NII, but not between clinical diagnosis and TRH test, was found. There was no correlation between DST and the severity of depression according to the Hamilton depression rating. The nosographic and the diagnostic specificities and sensitivities for the DST, TRH test and NII and DST and NII, a nosographic sensitivity of 50% and a nosographic specificity of 84% were found. Correspondingly, the diagnostic sensitivity was 43% and the diagnostic specificity was 88%. The DST and the TRH test were found of no value in the prediction of the response to antidepressive treatment. Mainly because of a low diagnostic sensitivity the NII, the DST and the TRH test are of limited value in the diagnosis of depressive disorders.     

Release of growth hormone, prolactin and somatostatin during perifusion of anterior pituitary and preoptic-medial basal hypothalamus from male and female rats

These experiments were designed to determine whether it is possible using in vitro perifusion to identify a sex difference in anterior pituitary (AP) release of growth hormone (GH) and, if so, to determine whether this difference is correlated with a sex difference in hypothalamic release or content of somatostatin (SRIF). Age-matched rats of both sexes were decapitated at approximately 09.00 h, and blood was collected for determination of non-stress plasma concentrations of GH. Each pituitary was rapidly removed and prepared for perifusion of the AP, and each preoptic-medial basal hypothalamus (PO-MBH) was removed and placed in a separate perifusion chamber. The effluent fractions from perifused APs were assayed for GH and prolactin (Prl), and those from PO-MBH blocks were assayed for SRIF. Non-stress plasma GH concentrations were similar in males and females. During perifusion, baseline GH release was higher (P less than 0.001) from male than from female APs. Release of GH from the APs of both sexes was similarly inhibited (P less than 0.001) by a 1-h administration of SRIF (10(-7) M), and high K+ (50 mM) caused larger (P less than 0.05) GH responses from male than from female APs. In contrast, baseline Prl release was higher (P less than 0.01) from female than from male glands, and Prl release was not affected by SRIF. Male and female PO-MBH tissues showed similar baseline release of SRIF and similar responses to high K+. After perifusion, GH content and concentration were higher in APs from males than from females, but SRIF content in the perifused male and female PO-MBH tissues was similar.(ABSTRACT TRUNCATED AT 250 WORDS)     

Chronic immunization of endogenous thyrotrophin-releasing hormone (TRH) in brain alters the behavioural response to pentobarbital and a TRH analogue

Rats were infused with purified thyrotrophin-releasing hormone (TRH) anti-serum i.c.v. for two weeks and the reversal of pentobarbital-induced anaesthesia, hypothermia and respiratory depression by central administration of a TRH analogue (CG 3509) was measured. After antibody infusion the anaesthesia time was more than doubled but the responses to CG 3509 were increased, suggesting a role for endogenous TRH in arousal mechanisms which is sensitized following chronic immunological blockade.     

Dexamethasone suppression test (DST) in relation to depressive somatic and suicidal manifestations

An investigation of 51 depressed inpatients showed a significant positive correlation between non-suppression in dexamethasone suppression test (DST) and the extent of depressive somatic symptoms. The DST did not differentiate between depressive suicidal and non-suicidal patients.     

Studies of growth hormone (GH), thyrotropin (TSH) and prolactin (PRL) secretion in anorexia nervosa.

(1) Studies of serum thyrotropin (TSH), growth hormone (GH) and prolactin (PRL) responses following TRH administration were performed in 7 subjects with anorexia nervosa (AN). (2) Five patients demonstratod significant increases in circulating GH from a mean of 15.6 ng/ml to a peak of 31.8 ng/ml 30 min after TRH. (3) Basal TSH concentrations were undetectable (< 2μU/ml) in all patients prior to stimulation but following TRH, significant elevations (ΔTSH > 6 μU/ml) in TSH were identified in 3/7 patients. (4) The largest elevations in TSH occurred in the two subjects in whom no GH rises were found, whereas blunted TSH rises were noted in 4/5 subjects who showed substantial GH secretory responses to TRH. (5) Basal PRL concentrations were normal and rose appropriately after TRH in all subjects. (6) These studies demonstrate that GH secretion can be provoked in AN by TRH similar to patterns in other states (acromegaly, uremia, protein-calorie malnutrition), characterized by elevated basal GH concentrations. (7) It is hypothesized that activated GH secretion may favor TRH responsivity of somatotrophs. (8) Obtundation of TSH secretion in AN, moreover, may be related to the augmented secretion of GH, since TSH secretion can be lowered by exogenous GH administration in man.     

Diplotypes of the human serotonin 1B receptor promoter predict growth hormone responses to sumatriptan in abstinent alcohol-dependent men.

BACKGROUND: Some studies have associated alcohol dependence (AD) with the human serotonin (5-HT)(1B) receptor (HTR1B). This investigation explored the functional responsivity of HTR1B in abstinent AD men using a sumatriptan challenge, while measuring genetic heterogeneity in the HTR1B promoter. METHODS: Abstinent AD men (n = 27) and abstinent men without any alcohol use disorder (n = 19) were administered 6 mg of sumatriptan succinate, subcutaneously. Plasma samples collected over the following 2 hours were assayed for growth hormone (GH) concentrations. His DNA was genotyped for the A-161T and T-261G polymorphisms of the HTR1B promoter and diplotypes determined. RESULTS: Integrated GH responses were predicted by interactions of AD and promoter diplotypes, as well as subject ethnicity. The final model accounted for nearly 35% of the variance in GH responses. Post hoc evaluation revealed that AD was associated with a blunting of GH secretion only among individuals with the most common HTR1B diplotype (TT/TT). CONCLUSIONS: A blunting of GH responses in abstinent AD men was observed only among those with the most common HTR1B promoter diplotype. Less common promoter diplotypes appeared protective. Controlling for genetic background is a useful augmentation of case-control pharmacological challenge strategies designed to elucidate the psychobiology of AD and other complex disorders.     

Effect of hypoglycaemia,TRH and levodopa on plasma growth hormone,prolactin, thyrotropin and cortisol in Parkinson's disease before and during therapy

Summary Thirteen drug-free and not severely affected patients with idiopathic Parkinson's disease underwent an insulin-hypoglycaemia test, a TRH test and a levodopa test. The responses of growth hormone, prolactin, cortisol and thyrotropin were measured, and retested under stable therapy with levodopa and benserazide. Mean basal and stimulated hormonal concentrations were in the normal range before and during therapy. Minor abnormalities were observed in individual cases, but did not indicate a hypothalamic dopamine deficit.     

Relationship between cerebrospinal fluid amine metabolites, neuroendocrine findings and personality dimensions (Marke-Nyman scale factors) in psychiatric patients

5-Hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) were measured in the spinal fluid of 45 women hospitalized in a psychiatric department for major depression (14 cases), schizophrenia (18 cases) and alcohol dependence (13 cases). Dexamethasone suppression tests were performed following CSF examinations in all patients, and TRH stimulation tests were also made in six subjects. All biological examinations were carried out in a drug-free state. The Marke-Nyman Temperament scale was administered to all patients as soon as severe psychotic disturbances subsided and sufficient cooperation was achieved, but no later than 10 days following biological examinations. The MNT was repeated after recovery to check reliability of the test results during an episode of a psychiatric disorder. CSF amine metabolite concentrations did not differ significantly in the three patient groups; postdexamethasone average cortisol levels were above the critical level (5 micrograms/dl) in each group, the highest values being found in major depression. One of the three MNT factors was inhomogeneous among diagnostic groups (validity: low in depression and alcoholism), but the other two also differed from a healthy control population. Correlation structure between biological and psychological variables was homogeneous throughout the diagnoses and a significant inverse correlation was found only between CSF 5-HIAA and the validity factor of MNT. Maximal TSH response to TRH stimulation correlated with both solidity and stability in the MNT scale. Since MNT results proved to be stable even during an illness episode, a possible link is suggested between personality traits and central serotonin metabolism.     

Lithium and twenty-four hour rhythms of serum corticosterone, prolactin and growth hormone in pigmented eye rats

Lithium, a widely used substance for the treatment of manic-depressive illness, has been reported to alter the phase relationships of a variety of biological rhythms. We have previously found that lithium affects serum melatonin differently in albino compared to pigmented eye rats. The present study was undertaken to investigate the effect of lithium on pituitary rhythms in pigmented eye rats. Six point 24 hour maps were generated throughout a 12 hour light/12 hour dark lighting regime on separate groups of individually housed adult male Long Evans rats (with pigmented eyes), maintained for six weeks on ad lib water and either normal lab chow or lab chow supplemented with 50 mM/Kg of lithium chloride. Animals were sacrificed by rapid decapitation with care to ensure that blood samples were obtained from subjects in the resting, undisturbed state. Plasma lithium levels were 0.57 ± 0.02 mEq/l. In comparison to normal controls, lithium treatment suppressed body weight by 19%, and increased water intake by 100%. Absolute corticosterone levels were not altered by lithium, but the 24-hour pattern was significantly changed. Growth hormone levels were significantly reduced by lithium treatment without alteration of the 24-hour pattern. Prolactin levels were significantly reduced by lithium and the normal 24-hour variation was attenuated. Comparison of these effects of lithium in pigmented eye rats with similar data from albino rats suggests that the effects on growth hormone, body weight and water intake were similar; however, the effects on prolactin and corticosterone differed. Since melatonin has been implicated in the regulation of prolactin and corticosterone rhythms, and this hormone is affected differently in the two types of rat, the observed effects of lithium on these hormone rhythms may be secondary to an alteration of the 24-hour pattern of melatonin by lithium.     

Central defects of autonomic function in secondary progressive multiple sclerosis: observations based on cardiovascular and growth hormone responses to clonidine

The haemodynamic, autonomic and hormonal effects of the centrally acting sympatholytic drug clonidine have been studied in 10 patients with secondary progressive multiple sclerosis (MS) and 10 age- and sex-matched normal subjects (controls). Detailed physiological studies, previously described in these 10 MS patients, indicated that none had postural hypotension or an abnormal Valsalva manoeuvre; six, however, had impaired responses to a range of pressor tests, suggestive of a central autonomic abnormality. In the controls after clonidine, there was a fall in blood pressure and superior mesenteric artery vascular resistance. Finger temperature and growth hormone levels rose. In the MS patients after clonidine, the haemodynamic responses varied. In five out of ten MS patients, as in the controls, there was a fall in blood pressure and superior mesenteric vascular resistance, while finger temperature rose. There was no haemodynamic response to clonidine in the other five MS patients. In eight out of ten MS patients there was no rise in plasma growth hormone levels after clonidine. The abnormal haemodynamic responses to clonidine, taken in conjunction with the previous physiological studies, suggest involvement of central sympathetic interconnections in five of the MS patients, probably as part of the demyelinating process. The impaired growth hormone response to clonidine occurred in a greater number of patients and may indicate lesions in the hypothalamus. These observations in MS patients, without overt clinical evidence of autonomic failure, indicate that the haemodynamic and growth hormone responses to clonidine may be an early indicator of autonomic dysfunction involving central autonomic centres and pathways.     

Chronic prolactin, gonadal and thyroid hormone treatments in vivo alter levels of TRH and muscarinic receptors in male and female rat tissues

Chronic subcutaneous administration of prolactin into female rats during proestrus led to a 20% (P < 0.05) decrease in retinal and a 32% (n = 20; P < 0.01) decrease in pituitary TRH receptors as compared to controls. In parallel experiments prolactin treatment during diestrus failed to influence TRH receptor levels in both tissues compared to vehicle-treated rats. Intraperitoneal injections of triiodothyronine for 8 weeks resulted in a selective 41% increase (P < 0.02) in retinal TRH receptor levels without any changes in the pituitary and 4 other brain regions. Administration of 17-β-estradiol for 2 weeks into male rats 1 month after castration resulted in a 68% increase (P < 0.02) in pituitary TRH receptor content without any changes in the retina, amygdala or hypothalamus. Testosterone administration for 2 weeks into castrated male rats 30 days post-castration did not alter TRH receptor content in the latter 4 tissues but caused a 27% (n = 10; P < 0.05) and a 40% increase (n = 5; P < 0.05) in muscarinic cholinergic receptor levels in the superior cervical ganglia and anterior pituitary gland, respectively. In conclusion, these data have demonstrated that chronic administration of exogenous hormones selectively up- or down-regulates TRH and muscarinic receptors in a region-specific manner depending on the physiological state of the animal and the tissue under study, and provide further new evidence for feedback hormonal control of these neurotransmitter receptors.     

Changes in serum thyroxine (T4) and serum thyroid stimulating hormone (TSH) during prolonged lithium treatment

We determined serum T4 and serum TSH serially in a cohort of patients given lithium treatment for up to 6 years; the total lithium exposure time was 409 years and the average serum lithium concentration 0.69 mmol/l. T4 showed a small and not significant fall at 6 months and returned to the pre-lithium level at 12 months. Hereafter, T4 rose gradually and after 6 years of lithium treatment T4 was 53% higher than the pre-lithium value. TSH was significantly increased at 6 and 12 months and then returned to the pre-lithium level. Eight patients required thyroxine treatment for lithium-induced hypothyroidism, i.e. 2 per 100 years of lithium exposure time. Single deviant values of T4 and TSH could be seen, followed by normal values. We suggest that TSH is determined at intervals during lithium treatment. It may be prudent to subject lithium-treated patients with abnormal thyroid values to re-examination and to abstain from starting thyroxine treatment on the basis of a single deviant value.