Blunted dexamethasone-induced growth hormone responses in acute mania

Dynamic endocrine testing using a variety of probes has revealed abnormalities of the somatotropic axis in bipolar mania. In health, acute administration of dexamethasone (DEX) results in the secretion of growth hormone (GH) by possibly inhibiting somatostatin tone. We elected to determine DEX/GH responses in acute mania. Eight male bipolar manics were compared with eight age-matched healthy volunteers. Four milligrams of oral DEX was administered at 0900h (time 0 min) and plasma samples for GH were taken at +60, +180, +240 and +300 min. Baseline samples for GH and cortisol were taken at −15 min and 0 min. Patients had higher basal cortisol levels (391.6 ± 89.4 nmol/l) as opposed to controls (138.0 ± 13.2 nmol/l) (paired t-test, t=4.68, DF=6, p < .0004). The mean ( ± SD) ΔGH (calculated as the maximum GH level relative to baseline) in the manic patients was 0.7 ± 0.8 ng/ml and in the healthy controls was 9.2 ± 4.3 ng/ml (paired t-test, t=−0.589, DF=6, p < .0001). In conclusion, patients with bipolar mania had lower DEX-induced GH responses in comparison to controls.     

Apomorphine stimulation of vasopressin- and oxytocin-neurophysins. Evidence for increased oxytocinergic and decreased vasopressinergic function in schizophrenics

Apomorphine challenge tests (0.5 mg SC) were performed in 14 normal male volunteers and in 9 male schizophrenic inpatients, drug-free for at least 2 wk. In the normal volunteers, apomorphine induced an increase of serum growth hormone (GH) (maximum at 40 min), of vasopressin-neurophysin (hN_PI) (maximum at 20 min), and oxytocin-neurophysin (hN_PII) (maximum at 20 min). The release of neurophysins was independent of digestive side effects. In the schizophrenics, the GH level and release pattern were similar to those in the controls. The basal level of hN_PI was reduced (t₀: 0.42±0.1 ng/ml in the schizophrenics and 0.66±0.05 ng/ml in the controls, p<0.02). In contrast, the basal level of hN_PII was increased (3.34 ± 0.04 ng/ml in the schizophrenics to 0.92±0.21 ng/ml in the controls, p=0.001). The response to apomorphine was blunted, with no significant release of hN_PI or of hN_PII. Although the hN_PII data are consistent with an increased dopaminergic tone, the psychopathological meaning of the increased basal oxytocinergic and decreased vasopressinergic functions remains to be defined.     

Influence of clenbuterol, a β-adrenergic agonist, on desipramine induced growth hormone, prolactin and cortisol stimulation

We report herein the effects of the β-adrenergic agonist clenbuterol on desipramine(DMI)-induced growth hormone (GH), prolactin (PRL) and cortisol secretion in healthy male subjects. In the first study, nine subjects were treated with either clenbuterol (0.04 mg, p.o.) or placebo. In the second study, 12 subjects received either DMI (50 mg, i.v.) alone or in combination with clenbuterol (0.04 mg, p.o.) given 60 min prior to DMI administration.

Clenbuterol alone had no influence on GH, PRL, or cortisol concentrations, compared to placebo. DMI alone caused GH stimulation (mean MAXIMUM = 15.7±3.4 ng/ml), which was significantly lower after combined administration of DMI and clenbuterol (mean MAXIMUM = 7.7±1.6 ng/ml) (p≤0.01). DMI-induced PRL and cortisol stimulation was not influenced by clenbuterol pretreatment.

These results indicate the inhibiting influence of noradrenergic β-receptors on GH stimulation.     

Relationships between fibrinogen, plasminogen activator inhibitor-1, and their gene polymorphisms in current smokers with essential hypertension

Background: To elucidate the role of some haemostatic gene polymorphisms and environmental factors, we studied fibrinogen (Fb), plasminogen activator inhibitor-1 (PAI-1), and tissue plasminogen activator (t-PA) levels with respect to Fb G455A and PAI-1 4G/5G gene polymorphisms in smokers and nonsmokers with essential hypertension. Material and methods: The study was done in 90 patients (including 30 smokers) with essential hypertension (HT) and 40 controls (including 8 smokers). Fb and PAI-1 genotypes were PCR identified. The groups did not differ significantly as to genotype frequencies. Results: When allele A455 carriers were compared, HT patients had significantly higher Fb (p=0.015) and t-PA levels (p=0.013). Comparison of 4G allele carriers (4G/4G homozygotes) revealed significantly higher Fb (p=0.045), PAI-1 (p=0.009), and t-PA levels (p=0.007) in HT patients than controls. Interactions of Fb and PAI-1 gene polymorphisms with smoking were disclosed in HT patients only. Allele A455-carrying HT smokers compared with nonsmokers had significantly higher t-PA (12.1±5.8 vs. 7.4±3.1 ng/ml; p=0.002) and tendency to higher Fb (3.36±0.74 vs. 2.95±0.70 g/l; p=0.075) levels. Higher Fb levels were disclosed in 4G/4G smokers than nonsmokers (3.31±0.81 vs. 2.84±0.85 g/l; p=0.064). Finally, in smokers, significantly higher levels of PAI-1 were found in 4G/4G (42.1±29.4 ng/ml) as compared with 4G/5G (18.6±13.7 ng/ml; p=0.025) and 5G/5G (14.4±10.8 ng/ml; p=0.044) genotypes. Conclusions: Smoking potentiates the prothrombotic effect of allele A455 and PAI-1 4G/4G genotype in untreated essential hypertension, reflected by increased levels of haemostatic risk factors and accelerated progression of cardiovascular diseases.     

Re-evaluation of L-tryptophan-stimulated human growth hormone secretion: A dose-related study with a comparison with L-dopa and apomorphine tests

Summary To find optimum dose for L-tryptophan (L-TP) to be used in growth hormone (GH) stimulation tests, a dose-related study on the effects of L-TP on human GH secretion was performed. 2, 5 and 8 g L-TP was given perorally in random order to 8 healthy male volunteers, and the GH response compared with values obtained after placebo. Furthermore, the L-TP test (performed with the 5 g dose) was compared with placebo, L-dopa and apomorphine tests. Each of these groups consisted of 24 male volunteers.In the dose-response part of the study, all doses of L-TP induced statistically significant stimulation of GH release: the mean peak GH level rose after 2 g L-TP from the mean basal level of 2.0±0.28 ng/ml to 8.2±1.8 ng/ ml (p<0.01), after 5 g L-TP from the mean basal level of 2.4±0.35 ng/ml to the mean peak level of 9.2±1.8 ng/ml (p<0.01), after 8 g L-TP from 2.7±0.30 ng/ml to 6.7±0.7 ng/ml (p<0.05) and after placebo from the mean basal of 1.8±0.28 ng/ml to 3.2±0.7 ng/ml (ns.). Although the GH responses to these three doses of L-TP did not statistically differ, there was a clear tendency to attenuated GH response to 8 g L-TP loading.In the material consisting all L-TP tests performed in our laboratory with 5 g dose of L-TP, 5 subjects out of 24 (20.8 %) failed to respond to L-TP (serum GH level <5.0 ng/ml). However, when comparing L-TP test with placebo, significant stimulation of GH release was observed (p<0.001). On the other hand, both L-dopa (p<0.05) and apomorphine (p<0.01) proved to be more potent stimulators of GH secretion in man. The peak GH levels after L-dopa and apomorphine occurred constantly, while the timing of the peak GH response to L-TP was more variable.The dose-response study demonstrates that the maximal responsiveness of GH secretion to L-TP loading is limited, and by no means comparable with the dopamine-controlled GH secretion. Because the avident decline in GH response to high-dose L-TP loading, a dose of 5 g seems most suitable to be used in human GH studies.     

Vitamin E improves fibrinolytic activity in patients with coronary spastic angina

Introduction: The fibrinolytic system has a major role as a defense mechanism against thrombus formation. Net fibrinolytic activity in plasma reflects the balance between tissue-type plasminogen activator and plasminogen activator inhibitor (PAI). PAI is the main factor determining overall fibrinolytic activity. Materials and methods: We examined the effects of oral administration of vitamin E, an antioxidant, on fibrinolytic activity and oxidative stress in patients with coronary spastic angina. Forty patients with coronary spastic angina were randomly assigned into two treatment groups, either vitamin E group (-tocopherol acetate, 400 mg/day) or placebo group by means of computerized system. PAI activity and thioredoxin, a marker of oxidative stress, levels were measured before and at the end of 1 month treatment. Results: Before treatment, the levels of PAI activity and thioredoxin were increased in patients with coronary spastic angina as compared with control subjects (n=17) (PAI activity levels: 13.6±1.4 vs. 7.6±2.2 IU/ml, p<0.05, thioredoxin levels: 22.8±1.7 vs. 16.0±1.4 ng/ml, p<0.05). In patients with coronary spastic angina, administration of vitamin E decreased both PAI activity and thioredoxin levels (PAI activity levels: 14.7±1.7 to 7.5±1.6 IU/ml, p<0.01, thioredoxin levels: 23.3±2.4 to 15.1±2.5 ng/ml, p<0.01), whereas placebo had no effect on these variables. Conclusions: Oral administration of vitamin E improved fibrinolytic activity and the improvement was associated with a decrease in oxidative stress. Administration of vitamin E is possible to be an effective adjunct therapy of coronary spasm in the absence of coronary atherosclerosis.     

Reduced dopamine function in depressed patients is related to suicidal behavior but not its lethality

Several lines of evidence suggest a role for dopamine in the control of suicidal behaviour. Previously, we suggested an involvement of D2-dopaminergic function in the biology of suicide by demonstrating a smaller growth hormone (GH) response to apomorphine, a dopaminergic agonist, in depressed patients who later died by suicide. The purpose of the present study was to assess GH response to apomorphine in major depressed in-patients with a history of highly lethal suicide attempt compared to depressed patients with a low lethal lifetime suicide attempt history and non-attempters. The study was performed in a sample of 26 male depressed in-patients with a history of suicide attempt compared to 26 male depressed non-attempters. We observed a significant difference between suicide attempters and non-attempters (for GH peak, 6.3+/-5.1 ng/ml vs 15.8+/-14.2 ng/ml, F=10.3, df=1, 50, P=0.002). Moreover, GH peak responses to apomorphine did not differ between depressed patients with a high lethal lifetime suicide attempt history and patients who made low lethal lifetime suicide attempt. In conclusion, the results of the present study support a role for dopamine in the biology of suicidal behaviour. More specifically, an impaired GH response to apomorphine could be a marker of suicide risk.     

Ultradian Rhythm of Growth Hormone Secretion in Unrestrained,Conscious Male Rabbits: Role of Endogenous Somatostatint†

The profiles of growth hormone (GH) secretion were examined by obtaining serial blood samples every 15 min for a 5 to 24 h observation period from freely-moving, conscious male rabbits chronically implanted with a right atrial cannula. The effects of restraint or surgical stress on GH secretion were also investigated in these animals. Four days after cannulation of the right atrium, plasma GH levels remained low without oscillation, during a 5 h observation period (1100 to 1600 h) with the mean (± SEM) value of 1.6±0.2 ng/ml. Individual rabbits exhibited a spontaneous, pulsatile GH secretion 7 days after the surgery. Mean 6 h GH levels were 5.6 ± 0.8 ng/ml at 7 days after the surgery, 6.3 ± 0.6 ng/ml at 14 days and 7.0 ± 1.2 ng/ml at 28 days. Therefore, the animals, 7 to 14 days after cannulation, were used to analyse the pulsatile pattern of GH secretion throughout 6 to 24 h. Two episodes of 45 min immobilization stress, separated by 75 min, caused a complete suppression of the spontaneous GH secretion (mean 6 h GH levels, 2.2 ± 0.1 ng/ml vs control, 5.0 ± 0.5 ng/ml, P<0.01). No surges appeared after the first restraint stress. In 14 non-treated rabbits, plasma GH levels fluctuated in an episodic manner throughout the study with the peaks of 14.2 + 0.7 ng/ml, the nadirs of 2.6 ± 0.2 ng/ml and the peak to peak intervals of 2.20 ± 0.17 h. The iv administration of normal goat λ-globulin (NGG) affected neither GH secretory patterns nor baseline levels of plasma GH. In contrast, the iv administration of anti-sornatostatin goat λ-globulin (ASG) caused a significant increase in the amplitude of plasma GH peaks (38.8±1.9 vs NGG-treated, 13.7 ± 0.8 ng/ml, P<0.001) as well as the trough level (13.5 ± 0.6 vs NGG, 2.9 ± 0.1 ng/ml, P<0.001) during a 24 h observation period. Also, ASG treatment increased numbers of plasma GH peaks per day (18.8±2.7 vs NGG, 12.2 ± 0.8, P < 0.05) with concomitant shortening of the peak to peak interval (1.25 ± 0.10 vs NGG, 2.03±0.12h, P<0.01). These findings suggest: 1) that GH is episodically secreted throughout the day in conscious male rabbits, 2) that surgical and restraint stresses suppress the spontaneous GH secretion, and 3) that endogenous somatostatin might rather play a tonic inhibitory role in GH release in conscious male rabbits, since ASG treatment resulted in sustained marked increases of plasma GH levels irrespective of the stage in GH pulsatile rhythm.     

Reduced dopaminergic activity in depressed suicides

Several data are available about the implication of the dopaminergic system in the control of inward-directed aggression. Previously, we suggested an involvement of D2-dopaminergic function in the expression of suicidal behavior by demonstrating a smaller growth hormone (GH) response to apomorphine, a dopaminergic agonist, in depressed patients with a history of suicide attempts in comparison to nonattempters. In the present study, the purpose was to analyze GH responses to apomorphine in depressive patients who later died by suicide. Our sample comprised eight male depressive inpatients who died by suicide within one year after hospitalisation. These patients were compared to 18 male major depressed inpatients who never attempted suicide. Mean GH peak responses to apomorphine differed significantly between suicide completers and controls (mean +/- SD): for GH peak, 7.6 +/- 4.1 ng/ml vs 18.9 +/- 14.2 ng/ml, U = 30, Z = -2.33, P = 0.02. Our results tend to confirm the role of dopamine in the biology of suicide in depression.     

A chronobiological study of melatonin and cortisol secretion in depressed subjects: plasma melatonin, a biochemical marker in major depression

The temporal organization of plasma melatonin and cortisol secretion was examined in healthy rested controls and in depressed patients: 11 patients suffering from a primary affective disorder (10 female, 1 male) and 8 male controls were studied over a 24-hr period; blood was collected at 2-hr intervals during the day at 1-hr intervals at night. Plasma melatonin and cortisol levels were determined by radioimmunoassay. In addition, melatonin was determined in plasma sampled at 3 AM in older male controls (n = 8) and in females (n = 10) at ovulation. The controls showed low or undetectable (less than 5 pg/ml) diurnal plasma melatonin levels and a very marked nocturnal rhythm (acrophase: 2.27 AM, mesor: 34.4 pg/ml, amplitude: 58.7 pg/ml). For the three control groups, no significant difference was observed in the nocturnal melatonin peak at 3 AM. The depressed patients also showed a significant melatonin rhythm but with lower amplitude (14.5 pg/ml) and mesor (19.1 pg/ml). The latter rhythm was not significantly phase-advanced with respect to the controls (acrophase at 1.18 and 2.34 AM, respectively). In 9 of the 11 patients, nocturnal melatonin secretion was less marked and frequently associated with hypercortisolemia. An additional episodic melatonin secretion was observed in the late afternoon in only two patients. In depressed patients, there was an increase in the mean cortisol secretion level (mesor at 13.6 micrograms/100 ml against 9.1 micrograms/100 ml in the controls), but the amplitude and the acrophase were not significantly modified. These data are discussed in terms of both the hypothalamus-pituitary-adrenal-epiphysis and aminergic abnormalities.     

Effect of apomorphine on growth hormone and prolactin secretion in schizophrenic patients, with or without oral dyskinesia, withdrawn from chronic neuroleptic therapy.

Serum growth hormone (GH) and prolactin (PRL) concentrations were measured after administration of the dopamine receptor agonist, apomorphine HC1 (0.75 mg subcutaneously), to 17 chronic schizophrenic patients, four of whom had an oral dyskinesia, who were withdrawn from chronic neuroleptic therapy for periods of two to 15 weeks, and in 21 control subjects (normal volunteers or physically healthy alcoholics not exposed to neuroleptics). Six of the schizophrenic patients, but none of the controls, had raised baseline levels of GH (greater than 6 ng/ml). After apomorphine all controls showed an increase in serum GH with a peak concentration of 9 ng/ml or more, whereas eight subjects withdrawn from neuroleptics showed an inadequate response (peak less than 6 ng/ml) and in two others an inadequate response was obtained on one of two trials. The peak GH concentration was significantly less after apomorphine in patients withdrawn from neuroleptics (11.90 +/- 3.19 ng/ml) compared with controls (20.80 +/- 2.11 ng/ml) (P less than 0.05). Among patients withdrawn from neuroleptics, those with an oral dyskinesia had significantly lower peak GH concentration 2.46 +/- 0.93 ng/ml) after apomorphine compared with those without (14.85 +/- 3.83 ng/ml) (P less than 0.05). There were no differences in serum PRL concentrations, before or after apomorphine administration, between patients withdrawn from neuroleptics and controls. In uncontrolled observations none of the four patients with an oral dyskinesia showed any worsening of the movement disorder after apomorphine. These data provide no evidence for supersensitivity of dopamine receptors in chronic schizophrenic patients withdrawn from chronic neuroleptic therapy.     

Alpha-2-adrenoreceptors in depressed suicide attempters: relationship with medical lethality of the attempt

Several lines of evidence tend to suggest a role for noradrenaline, and more specifically alpha-2-adrenoreceptors, in the biology of suicidal behavior. The purpose of this study was to assess the growth hormone (GH) response to clonidine, an alpha-2-adrenergic agonist, in majorly depressed inpatients with a history of highly lethal suicide attempt compared to depressed patients with a history of low lethal suicide attempt and nonattempters. Our sample included 20 male depressed inpatients with a history of suicide attempt compared to 20 male depressed nonattempters. We did not observe any significant difference between suicide attempters and nonattempters for GH peak values (2.4 +/- 2.9 vs. 4.1 +/- 3.7 ng/ml; F = 2.52, d.f. = 1, 38, p = 0.12). Moreover, GH peak responses to clonidine were not related to the degree of lethality of the attempt. The results of the present study do not support a major role for noradrenaline in the biology of suicidal behavior.     

Growth hormone (GH) response to clonidine and growth hormone releasing factor (GRF) in normal controls

To investigate the relationship between the plasma growth hormone (GH) response to provocative challenge with the hypothalamic peptide growth hormone-releasing factor (GRF) and the alpha 2-adrenergic agonist clonidine, we administered GRF (1 microgram/kg), clonidine (2 micrograms/kg), and placebo to 21 healthy normal controls (13 men and eight women). Both clonidine and GRF caused significant increases in plasma GH levels over baseline. The peak GH-responses to GRF and clonidine were similar (GRF = 8.7 +/- 6.7 ng/ml; clonidine = 6.5 +/- 5.9 ng/ml; Wilcoxon test: s = 361, z = -1.31, p = NS). The GH responses to GRF and clonidine were significantly correlated (rs = 0.62, n = 20, p = 0.004). Unexpectedly, we found that five of the 21 (26%) normal controls had no GH secretory response to either GRF or clonidine. There was a modest gender effect with clonidine (men greater than women; p less than 0.06) and a negative correlation between GH secretion and age with both GRF and clonidine. Neither GRF nor clonidine had an effect on cortisol levels (DRUG x TIME interaction: F(8,152) = 0.60, p = NS). These findings are consistent with animal studies suggesting that the GH response to clonidine is mediated by GRF. The age and gender effects underscore the importance of careful matching for these factors in studies measuring the GH secretory response.     

Growth hormone response to apomorphine in panic disorder: Comparison with major depression and normal controls

Several lines of evidence suggest that dopamine might be involved in anxiety states. In the present study we assessed the growth hormone (GH) response to 0.5 mg apomorphine (a dopaminergic agonist) in 10 male drug-free inpatients meeting Research Diagnostic Criteria for panic disorder who were compared with 10 male major depressive inpatients and 10 male normal controls. The three groups differed significantly in the GH peak response (mean ± SD): 27.8±12.5 ng/ml in panics, 5.4±4.0 ng/ml in major depressives, and 25.8±11.3 ng/ml in normal controls (F(2,27)=15.3;P=0.00003). Although there were significant differences between panics and major depressives (P=0.00004), and between major depressives and controls (P=0.00004), panics did not significantly differ from controls. These results do not support the hypothesis of an overlap between panic and affective disorders, and suggest that the hypothalamo-GH-somatomedin axis could be intact in panic disorder.     

Plasma homovanillic acid and treatment response in a large group of schizophrenic patients

Plasma levels of homovanillic acid (pHVA), a metabolite of dopamine, were measured in ninety-five Chinese schizophrenic patients free of neuroleptics for at least four weeks. These patients were treated with classical antipsychotics for six weeks. Pretreatment pHVA was positively correlated with the subsequent clinical response (r=0.408, p<0.0001). Good responders (BPRS improvement 50%, n=47) had higher pretreatment pHVA levels than poor responders (BPRS improvement < 50%, n=48) (15.7±8.4 ng/ml versus 9.9±3.7 ng/ml, p<0.0001). A higher than 15 ng/ml pretreatment pHVA level was associated with a more consistent clinical response to the subsequent treatment. Using a pHVA level of 12 ng/ml as a demarcation point, 72% of patients (34 of 47) who had pHVA 12 responded whereas 65% (31 of 48) who had <12 did not respond (chi-square=13.02, p<0.0001). These results suggest that higher pretreatment pHVA levels may predict a better clinical response to antipsychotics. Based upon the pHVA findings, two hypothetical subtypes of schizophrenia are proposed.     

Role of dopamine in non-depressed patients with a history of suicide attempts.

Several data are available about the implication of the dopaminergic system in the control of inward-directed aggression. Previously, we suggested an involvement of D2-dopaminergic function in the expression of suicidal behavior by demonstrating a smaller growth hormone (GH) response to apomorphine, a dopaminergic agonist, in depressed patients with a history of suicide attempts in comparison to non-attempters. In the present study, in order to test this hypothesis, GH responses to intravenous apomorphine were measured in non-depressed patients with a history of suicide attempts. The study was performed in 17 non-depressed male patients with a score less than 12 on the 17-item HAMD. The patients were subgrouped into suicide attempters (N = 7) and non-attempters (N = 10). Mean GH peak responses to apomorphine differed significantly between suicide attempters and non-attempters: (mean +/- SD) for GH peak, 10.4 +/- 8.2 ng/mL vs 27.3 +/- 13.1 ng/ml, F = 9.0, P = 0.009. In conclusion, dopaminergic disturbances seem to play a role in the biology of inward-directed aggression in non-depressed patients.     

Different effects of baclofen on LH and cortisol responses to naloxone in normal men

The possible involvement of GABAergic B receptors in the control of LH and ACTH/cortisol secretion in response to naloxone was evaluated in seven normal men. subjects were tested with naloxone (4 mg IV bolus plus 10 mg infused over 2 hr) with or without previous treatment with the γ-aminobutyric acid (GABA)-ergic B receptor agonist, baclofen (5, 10 or 15 mg PO 30 min before naloxone). In additional experiments, six normal men were tested with 15 mg baclofen or placebo 30 min before a 2-hr infusion of normal saline. Plasma cortisol levels rose 70% in response to naloxone. The naloxone-induced cortisol rise was not modified by pretreatment with baclofen (5, 10 or 15 mg). Plasma LH concentrations rose 66% in response to naloxone. When the lowest dose of baclofen (5 mg) was administered, the LH response to naloxone remained unchanged. In contrast, 10 mg baclofen produced a significant reduction, and 15 mg baclofen completely abolished the naloxone-induced LH rise. The administration of baclofen or placebo alone did not change basal plasma levels of cortisol and LH. These data suggest that, in normal men, GABA B receptors participate in the endogenous opioidergic control of LH secretion, but not of ACTH/cortisol secretion.     

Growth hormone release after desipramine in depressive illness

Summary The effect of i.m. administration of 75 mg of desipramine on growth hormone (GH) secretion was investigated in a sample of 87 patients with major depressive disorders and in 31 normal controls. The GH response was lower in depressed females compared to depressed males, but no such difference was present in controls. In the premenopausal female group, GH response was significantly lower in depressed patients than in controls. No significant difference was found between normal males and male depressed patients. In the premenopausal group, no difference emerged between endogenous and nonendogenous depressed women.     

Neuroendocrine effects of citalopram infusion in anorexia nervosa

Because of the role of serotonin (5HT) in regulating food intake and mood, several studies have focused their attention on the assessment of serotonergic activity in eating disorders, and in particular in anorexia nervosa, but the results have been inconsistent. Citalopram, a highly selective 5HT reuptake inhibitor, has been recently reported as a neuroendocrine probe to assess the serotonergic function in physiological and pathological conditions. We evaluated the adrenocorticotropic hormone (ACTH), cortisol, prolactin (PRL) and growth hormone (GH) secretion during placebo or citalopram IV infusion (20 mg over 120 min), in six women with anorexia nervosa restricter type, and in six healthy women, in order to test the hypothesis that this neurotransmitter system is abnormal in this group of patients. ACTH and PRL secretion was higher during citalopram infusion compared to placebo (p<0.05) in both groups, while cortisol secretion was higher during citalopram infusion only in healthy controls (p<0.05), but not in anorexic patients. GH levels were unaffected by citalopram in both groups. These results demonstrate that serotonergic activation by citalopram affects corticotroph and lactotroph but not somatotroph secretion in anorexic as well as in normal subjects. Our preliminary findings do not support the existence of remarkable alterations in the serotonergic control of anterior pituitary function in anorexia nervosa, while there seems to be an impairment of the adrenal function in this group of 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.