Hypothalamic-pituitary dopaminergic function in hepatic failure in man

Summary The growth hormone (GH) response to apomorphine HCl (Apo) (0.75 mg sc), a dopamine (DA) receptor agonist, was assessed in healthy chronic alcoholics without cirrhosis (N=20) and in patients with alcoholic cirrhosis both with (N=5) and without (N=14) hepatic encephalopathy (HE). A significant number of cirrhotic patients with (P<0.004) and without (P<0.002) HE had an impaired GH response (peak increment<5 ng/ml) compared with non-cirrhotic individuals. An impaired GH response was independent of the presence of HE. The magnitude of the GH response was unrelated to plasma oestrone, oestradiol, or progesterone concentrations but was significantly correlated with plasma testosterone levels (P<0.01). None of the patients with an abnormally low testosterone concentration showed a normal GH response. None of the subjects with HE showed an arousal response to Apo. These results suggest that DA receptor sensitivity is decreased in liver cirrhosis and that this decrease is related to inadequate circulating levels of testosterone. The occurrence of HE is independent of impaired DA function. The present study only evaluates DA function in the hypothalamic-pituitary axis and therefore may not reflect changes in other regions of brain.Presented in part at the International Symposium on Neuroendocrine Correlates in Neurology and Psychiatry, Rome, December 8–9, 1978.     

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of apomorphine on growth hormone and prolactin secretion in schizophrenic patients, with or without oral dyskinesia, withdrawn from chronic neuroleptic therapy.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HC1 (0.75 mg subcutaneously), to 17 chronic schizophrenic patients, four of whom had an oral dyskinesia, who were withdrawn from chronic neuroleptic therapy for periods of two to 15 weeks, and in 21 control subjects (normal volunteers or physically healthy alcoholics not exposed to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all controls showed an increase in serum GH with a peak concentration of 9 ng/ml or more, whereas eight subjects withdrawn from neuroleptics showed an inadequate response (peak less than 6 ng/ml) and in two others an inadequate response was obtained on one of two trials.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.     

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.     

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 and somatomedin-C in bulimia

Somatomedin-C (SOM-C) concentrations are regulated by circulating growth hormone (GH) concentrations; however, other factors, such as nutrition, also influence SOM-C concentrations. We evaluated the GH-SOM-C axis in seven normal-weight female bulimics one day after hospital admission, and in seven age-, sex-, and weight-matched normal controls. Subjects were medication-free for at least one month. Fasting morning serum GH concentrations were higher in all bulimics (range 2.5-13.3 ng/ml) than in all controls (range less than 1.0-1.8 ng/ml). The mean (+/- SD) maximum GH response to TRH (500 micrograms) was greater in the bulimics (12.9 +/- 4.9 ng/ml) than in the controls (3.7 +/- 2.7 ng/ml) (p less than .001). Despite this GH elevation, the mean (+/- SD) SOM-C concentration was comparable in the bulimics (2.0 +/- 0.6 U/ml) and the controls (1.6 +/- 0.8 U/ml). This suggests that SOM-C generation is resistant to the elevated circulating GH in bulimia and that SOM-C is not inhibiting GH secretion in the pituitary-hypothalamic axis.     

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.     

Mesotocin in the brain and plasma of an Australian marsupial, the brushtail possum (Trichosurus vulpecula)

Oxytocic peptides extracted from the brain and plasma of the brushtail possum, Trichosurus vulpecula, were separated by reverse-phase high pressure lipid chromatography (HPLC) and quantified by specific radioimmunoassays for oxytocin (OT) and mesotocin (MT). The pituitary, hypothalamus and cerebral cortex were found to contain MT only in quantities of 3.9 +/- 0.2 (SE) ug, 17.6 +/- 0.6 ng and 21.0 +/- 2.6 ng respectively. The plasma concentration of MT varied according to the degree of stress of the possum. In anaesthetized animals values of 39.7 +/- 9.7 pg/ml (11 males) and 31.5 +/- 12.9 pg/ml (6 females) were obtained; in four conscious catheterized animals, 9.4 +/- 6.3 pg/ml. Samples taken from three anaesthetized animals during exsanguination contained 271 +/- 102 (SD) pg MT/ml. It was concluded that hypothalamic and extra-hypothalamic MT is present in the marsupial brain and that as in placental mammals, stress stimulates the secretion of mesotocin.     

Sleep, clonidine, and their interactive effect on growth hormone secretion in normal men

Central alpha 2-adrenergic function is often inferred from the growth hormone (GH) response to clonidine, despite the drug's known hypnotic effect and the accepted cholinergic mechanism for sleep-related GH secretion. We examined the effect of daytime sleep on GH secretion in normal men taking placebo or clonidine orally, using a two-group blind design (placebo, clonidine; n = 9 each). Each subject participated in two morning sessions monitored by polysomnography: wake (sleep actively prevented) and sleep (subjects asked to sleep for 3 hr after receiving placebo or clonidine). Blood samples were drawn at times -15 min, 0, and every 30 min for 3 hr after the test dose was given. The total sleep time was similar for both groups. The placebo/wake group had lower GH responses than the other three groups. None of the GH responses in the clonidine/sleep group were significantly different from those in the placebo/sleep group; and the peak GH micrograms/L, mean +/- SD) was 16.9 +/- 10.9 vs. 14.6 +/- 10.5, respectively. We conclude that the GH response to clonidine may not be indicative of alpha 2-adrenergic function if sleep is permitted during the test.     

Effect of domperidone on apomorphine-induced growth hormone secretion in normal men

Summary Domperidone, a peripheral dopamine (DA) receptor blocker which poorly crosses the blood-brain barrier and which is inactive towards dop-amine-sensitive adenylate cyclase, in a dose (100g/kg) sufficient to increase serum prolactin levels at least 5-fold, decreased the growth hormone (GH) response to the DA receptor agonist, apomorphine HC1 (Apo) (0.5 mg s.c.) in each of six normal men examined. The mean GH increment at 30,45, 60 and 75 min following Apo injection, the mean individual peak increment and the mean individual GH secretion (ng min) was significantly decreased by domperidone pretreatment (p<0.05–p<0.02). These results indicate that in man Apo stimulates GH secretion by an effect on DA receptors which are not linked to adenylate cyclase and which are situated at a locus in the hypothalamic-pituitary axis that lies outside the blood-brain barrier.     

Reduction of GH response to the GABA-B agonist baclofen in patients with major depression

In order to establish whether alterations in the GABAergic control of GH secretion occur in male patients with major depression, the GH response to the GABAergic-B agonist baclofen (10 mg at 0830h) or to placebo was tested in 9 depressed men and in 10 age- and weight-matched male normal controls.

The basal concentrations of GH were significantly lower in the depressed patients (0.87± 0.69 ng/ml) than in the normal controls (1.57±0.33 ng/ml) (p=0.011) and were not modified by the administration of placebo. The administration of baclofen induced a striking, significant increase in GH concentrations in the normal controls (mean peak at 90 MIN=6.4±1.5 ng/ml). In contrast, a slight, nonsignificant GH increase occurred in the depressed patients after baclofen (mean peak at 90 MIN=1.57±1.45 ng/ml). The GH response was significantly lower in the depressed than in the control subjects (p<0.001). These data indicate the presence of reduced GABAergic control of GH secretion in male depressed patients.     

Ghrelin administered in the early morning increases secretion of cortisol and growth hormone without affecting sleep

Ghrelin and growth hormone (GH) releasing hormone (GHRH) both stimulate GH secretion and slow wave sleep (SWS), whereas ghrelin increases, and GHRH decreases cortisol in males. However, GHRH's effect on sleep and cortisol was abolished, on GH mitigated, when administered in the early morning, possibly due to counteracting corticotropin releasing hormone (CRH). Aim of this study was to investigate ghrelin's influence on sleep, GH and cortisol when administered in the early morning. Nocturnal (2000-1000 h) GH and cortisol patterns and polysomnography (2300-1000 h) were determined in 12 healthy males (25.3+/-3.2 yr) twice, receiving 50 microg ghrelin or placebo at 0400, 0500, 0600, and 0700 h, in this single-blind, randomized, cross-over study. The first ghrelin bolus caused the strongest (38.7+/-6.5 ng/ml, placebo: 0.4+/-1.1 ng/ml), second and third smaller, the fourth no GH peak. GH levels remained significantly (p<0.05) higher from 0420-0740 h in the ghrelin condition. Comparably, the first ghrelin bolus caused the strongest cortisol response (156.0+/-12.6 ng/ml; placebo: 78.0+/-10.5 ng/ml). Cortisol was significantly higher from 0440 to 0540 and at 0720 h and decreased thereafter to significantly lower levels (0820-0840 h). Sleep variables did not differ in both conditions. In contrast to GHRH, ghrelin's stimulatory effects were apparently not counteracted (GH), and enhanced (cortisol), respectively, by high CRH in the second half of night.     

Neuroendocrine evaluation of catecholaminergic neurotransmission in mania

Several lines of evidence suggest catecholamine overactivity (noradrenergic and/or dopaminergic) in mania. We studied the growth hormone (GH) response to clonidine (an alpha-adrenergic agonist) and apomorphine (a dopaminergic agonist) in seven inpatients meeting Research Diagnostic Criteria for mania. They had been completely drug free for at least 3 months before the neuroendocrine procedures and were age- and sex-matched to seven major depressive and seven minor depressive inpatients, drug free for at least 2 weeks. GH was assayed every 20 min for 40 min before and 120 min after either clonidine (0.15 mg i.v.) or apomorphine (0.5 mg s.c.), with an interval of at least 2 days between the tests. The three groups differed significantly in the GH peak response: after clonidine (mean +/- SD), 3.2 +/- 2.4 ng/ml in manics, 3.2 +/- 2.4 ng/ml in major depressives, and 13.2 +/- 8.7 ng/ml in minor depressives; after apomorphine, 10.5 +/- 7.4, 3.2 +/- 1.9, and 26.9 +/- 15.8, respectively. While there were significant differences between manics and minor depressives and between major and minor depressives after both clonidine and apomorphine, manics did not significantly differ from major depressives on either test. These results do not provide neuroendocrine support to the catecholaminergic hypothesis of manic disorders.     

Induction of tolerance of dopaminergic responses in man

Schizophrenia may reflect a sensitization of dopaminergic (DA) function. Apomorphine (Apo), a DA receptor agonist, induces both sensitization and tolerance of DA function in rodents depending on dose intervals. We investigated sensitization and tolerance to Apo in healthy male volunteers. After a period of acclimatization to the experimental setting (Day 1) subjects were assigned randomly to two groups: Group A subjects received seven injections of placebo (physiological saline) (PLA) and Group B subjects received seven injections of Apo HCl (7 mug/kg sc) under double-blind conditions at 2 h intervals commencing at 0930 hours (Day 2) after an overnight fast. Twelve hours after the seventh injection, i.e. on Day 3, after an overnight fast all subjects received an injection of Apo. Serial samples of blood commencing at 0900 hours were drawn after the first and last injection in both groups for assay of growth hormone (GH), prolactin (PRL) and cortisol by radioimmunoassay; sleepiness was measured using the Analog Sleepiness Rating Scale and yawning recorded by video recorder. The GH response in Group B (N = 8) was (a) decreased after the eighth injection of Apo compared with the first injection of Apo (P = 0.03) and (b) decreased after the eighth injection of Apo compared with the first injection of Apo in Group A (N = 10) (P = 0.001). The number of yawns in Group B was significantly decreased after the eighth injection of Apo compared with the first injection of Apo (P = 0.042). PRL, cortisol and sleepiness were not significantly different between the first and eighth injection of Apo. Sensitization was not observed in any of the measures studied. These results are compatible with induction of acute tolerance of DA-mediated GH and yawning responses. The method used provides a safe pharmacological paradigm to examine plasticity of DA mechanisms in man. Results are discussed in the context of possible therapeutic implications for schizophrenia.     

Apomorphine in the evaluation of dopaminergic function in man

1. Apomorphine (Apo), a short acting dopamine (DA) receptor agonist, stimulates growth hormone (GH) secretion, decreases prolactin secretion, induces yawning, penile erections and other physiological effects in man. An effect on behavior, movement disorders and alcoholism has also been described. 2. Apo-mediated responses are used to evaluate DA function in psychiatric and neurological disorders. Many of the studies in schizophrenia using the GH response to Apo as an index of central DA function are difficult to interpret because of failure to control for key variables. 3. The GH response to Apo is a useful system to evaluate the effects of various drugs including peptides which may not cross the blood brain barrier on DA function in man. 4. Apo is a potent sedative. Specific antimanic, antischizophrenic, and anticraving effects in alcoholics have not been convincingly demonstrated. Side effects of Apo and failure to use active placebo make double-blind studies difficult. 5. Apo improves parkinsonian symptoms and certain forms of reflex epilepsy but beneficial effects in other involuntary movement disorders requires further documentation. 6. Apo may be a useful agent to evaluate DA function in impotent patients and predict a therapeutic response to long-acting dopaminergic agents. 7. Impairment of DA function may play a role in diabetic impotence. 8. The development of a simple polygraphic method to monitor the yawning response to Apo may facilitate clinical studies on the basic physiology of yawning in man and the use of the yawning response as a measure of central DA function in schizophrenia and other clinical disorders. 9. The use of Apo with 18F-fluorodeoxyglucose positron emission tomography to examine regional DA function in man opens up a promising area of research. 10. Though long-acting orally active aporphine DA agonists and antagonists have been developed the problem of tolerance may limit their therapeutic potential.     

Thyrotropin releasing hormone uptake into serum and cerebrospinal fluid following intravenous or subcutaneous administration

Intravenous thyrotropin releasing hormone (TRH) was administered to 6 amyotrophic lateral sclerosis (ALS) patients at the dose rate of 10 mg/kg. Blood samples were obtained prior to and at 10, 20, 40, 60, and 120 min during the TRH infusions. Lumbar punctures were performed at 90 min following the start of infusion. The mean serum TRH concentration rose from 0.03 +/- 0.02 (SD) to 17 +/- 2 ng/ml by 60 min and remained constant to 120 min. The mean CSF TRH concentration rose 10-fold from 0.02 +/- 0.01 to 0.2 +/- 0.02 ng/ml at 90 min and increased further to 0.5 +/- 0.2 ng/ml at 120 min. Subcutaneous TRH was administered to 4 ALS patients at 2.5 mg/kg and to 5 ALS patients at 5.0 mg/kg. The mean serum TRH concentration increased to 1.4 +/- 0.6 ng/ml (2.5 mg/kg) and 3.2 +/- 1.1 ng/ml (5.0 mg/kg) by 60 min. The mean CSF TRH concentration at 60 min increased to 0.3 +/- 0.08 ng/ml following 2.5 mg/kg TRH and 0.8 +/- 0.04 ng/ml following 5.0 mg/kg TRH. TRH entry into the CSF is comparable following subcutaneous or intravenous administration.     

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.     

Body weight gain after administration of antipsychotic drugs: correlation with leptin, insulin and reproductive hormones

Excessive body weight gain, hyperprolactinemia and low gonadal steroid serum levels are often observed during chronic administration of antipsychotic drugs (AP). Clinical and experimental findings suggest that leptin, the peptidic hormone involved in long-term body weight regulation, and reproductive hormones are interrelated. Therefore, we assessed circulating leptin levels in healthy, lean women (n = 12) and men (n = 7) before and after short-term administration of the AP sulpiride (SUL, 200 mg/day). In addition, we studied psychotic obese (n = 9) and lean women (n = 13) under chronic treatment with diverse AP. No significant weight changes were observed after SUL administration in healthy women--initial weight: 54.9+/-2.6 Kg; final weight: 55.04+/-2.6, NS. Leptin levels did not change either: 11.9+/-1.5 ng/ml. vs. 10.6+/-1.3, NS. By contrast, a small, but significant weight gain was found in SUL-treated men--60.6+/-1.9 Kg. vs. 61.3+/-2.1, p = 0.004. Leptin and insulin levels were significantly higher after SUL administration--leptin: 2.77+/-0.22 ng/ml. vs. 13.9+/-2.5, p=0.035; insulin: 3.59+/-0.17 mIU/ml vs. 8.81+/-0.81, p = 0.0001. In these subjects, leptin levels positively correlated with body weight change (p = 0.006), and serum prolactin change (p = 0.001). Obese psychotic women (Body Mass Index, BMI, Kg/m2 = 31.5+/-1.03) displayed higher leptin levels than non-obese psychotic women (BMI = 25.5+/-0.52): 26.8+/-4.8, vs. 12.8+/-3.4 ng/ml, p = 0.006. In these women, a significant positive correlation was found between leptin levels and BMI (p = 0.0001), and between leptin and basal insulin levels (p = 0.001). These results show that the expected circulating leptin elevation which is observed when body weight raises, is preserved in people treated with AP drugs.     

Altered nocturnal growth hormone (GH) secretion in obsessive compulsive disorder

Nocturnal patterns of growth hormone (GH) in obsessive compulsive disorder (OCD), which is physiologically released predominantly during the first half of night, have not been reported. However, altered GH responses to pharmacological challenges suggest a disturbed function of the somatotropic axis in OCD. In this study, nine inpatients with a DSM-IV diagnosis of OCD without comorbid major depression (Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score >15; HAMD-21 total score 16) and 9 healthy matched controls were included. Blood of patients (7 males, 31.8+/-9.3 years, Y-BOCS: 27.3+/-4.3, HAMD-21: 13.3+/-1.9) and controls (7 males, 31.6+/-9.1 years) was drawn every 20 min between 2300 and 0700 h during sleep using a long catheter for later GH analysis. Mean plasma GH levels peaked at 0040 h, however this peak was significantly blunted in patients (maximum 4.3+/-1.5 ng/ml) compared to controls (maximum 12.3+/-4.0 ng/ml; p<0.05). In patients but not controls two other, smaller peaks were observed (0220 and 0620 h). In patients but not in controls, GH values exceeding maximum GH values of the peak at 0040 h were observed already at 2300 h or during the second half of night. In conclusion, our results indicate that the nocturnal GH secretion in patients with OCD is altered compared to controls.     

Ghrelin enhances the nocturnal secretion of cortisol and growth hormone in young females without influencing sleep

Ghrelin was shown to increase slow wave sleep (SWS) and the secretion of growth hormone (GH) and cortisol in young males. In terms of sleep, such information for females, however, is lacking. Therefore, polysomnographies were recorded (23:00-07:00 h) and nocturnal (20:00-07:00 h) secretion profiles of GH and cortisol were determined in 10 healthy females (24.9+/-2.4 years, body mass index: 21.2+/-1.1) twice, receiving four boluses of 50 microg ghrelin or placebo at 22:00, 23:00, 00:00, and 01:00 h, in this single-blind, randomized, cross-over study. No significant differences of conventionally or quantitatively analyzed sleep were observed between ghrelin and placebo condition. First administration of ghrelin caused a marked mean increase of GH by 53.3 to 64.4+/-14.2 ng/ml (placebo: 5.9+/-1.5 ng/ml) and cortisol by 54.2 to 96.4+/-15.3 ng/ml (placebo: 27.5+/-4.7 ng/ml). The following ghrelin injections were associated with smaller increases of GH and cortisol. In the ghrelin condition, GH plasma levels remained significantly (P<0.05) higher from 22:20 to 02:00 h and cortisol plasma levels from 22:20 to 02:20 h. In contrast to findings in young men, ghrelin did not affect sleep in young women, indicating a sexual dimorphism. In accordance with the findings in young men, ghrelin stimulated secretion of GH and cortisol.     

Stereospecificity of the dopamine receptor mediating the growth hormone response to apomorphine in man

Summary The stereospecificity of the D-2 receptor mediating the growth hormone (GH) response to apomorphine (Apo) and the D-2 receptor regulating prolactin (PRL) secretion were investigated in 10 normal men by examining the effects of cis-flupenthixol (cis-Fx) and trans-flupenthixol (trans-Fx). cis-Fx (1 mg six hourly times four doses) antagonized the GH response to Apo HCl (0.5 mg sc) and increased basal serum PRL concentrations whereas the transisomer showed no effect. These findings (a) provide further evidence that the GH response to Apo is mediated by stimulating dopamine (DA) receptors, and, (b) demonstrate stereospecificity of the DA receptor mediating the GH response to Apo and the DA receptor regulating PRL secretion.