Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects on GH and PRL secretion of several pharmacological agents known to modify central neurotransmitter action were determined in unanesthetized male rats. Phenoxybenzamine, an alpha-adrenergic blocker (5 mg/kg iv), abolished episodic GH secretion and caused elevation of serum PRL levels. Propranolol, a beta-adrenergic blocker (5 mg/kg iv), had no effect on GH secretion and caused a small but significant depression in PRL levels. Parachlorophenylalanine methyl ester, an inhibitor of tryptophan hydroxylase (300-350 mg/kg ip), resulted in significant inhibition of GH pulsatile secretion and suppressed PRL levels. Methysergide hydrogen maleinate (25 mg/kg iv), a serotonin receptor antagonist, also inhibited GH secretion, but produced a transient stimulation in PRL levels. Atropine sulfate (2 mg/kg iv) caused significant suppression in GH secretion, but had no effect on PRL. Picrotoxin, a gamma-aminobutyric acid antagonist, in a subconvulsive dose of 1-3 mg/kg iv, also depressed GH episodic secretion but did not affect PRL levels. These results indicate that several neurotransmitters, i.e., norepinephrine, serotonin, acetylcholine, and gamma-aminobutyric acid, found in high concentration in the hypothalamus, influence GH and PRL secretion.
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PMID:Neuropharmacological regulation of episodic growth hormone and prolactin secretion in the rat. 3 92

The effects of the ergoline derivative, lergotrile mesylate, on the serum levels of PRL, GH, TSH, LH, FSH, cortisol, and blood sugar were studied in six normal males. The effects of lergotrile mesylate on the serum levels of GH and PRL were also studied in eight patients with acromegaly and in two with idiopathic hyperprolactinemia. In the normal subjects, 2 mg oral lergotrile lowered basal PRL levels after 90 min and markedly impaired the PRL response to TRH (200 micrograms iv); the mean peak value +/- SE was 8.3 +/- 1.1 micrograms/liter, compared to the control value of 66.6 /+- 11.3 micrograms/liter. Lergotrile raised serum GH levels in five of the six subjects to peaks of 8-49 micrograms/liter, compared to 2-8 micrograms/liter after placebo. In three subjects, the GH response to lergotrile was attenuated by the prior administration of the dopamine antagonist, metoclopramide (10 mg orally). Lergotrile had no effect on FSH and LH levels under basal conditions or after the gonadotrophin-releasing hormone (GnRH; 100 micrograms iv). Circulating TSH levels were unaltered basally but impaired after TRH. Blood sugar levels were unaltered; serum cortisol was elevated in five of six subjects; there was a brief depression of diastolic blood pressure, but no change in pulse rate. The side effects after lergotrile were variable, with drowsiness as a consistent feature. These actions are similar to those of bromocriptine (an ergot derivative treatment of hyperprolactinemia and acromegaly, to suppress PRL and GH secretion, and in parkinsonism. Therefore, it may be expected that lergotrile could fulfill these clinical uses; however, in the studies comparing the effects of single oral doses of lergotrile (2 mg) and bromocriptine (2.5 mg) on GH and PRL secretion in patients with acromegaly and hyperprolactinemia, lergotrile in the dose used has been found to have an earlier onset and shorter duration of action.
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PMID:Effect of the dopamine agonist, lergotrile mesylate, on circulating anterior pituitary hormones in man. 4 63

Psychopathological picture of depression and the conduct of some hormone tests vs the therapeutic response to thymoleptics were examined. On the grounds of some diagnostic criteria, 84 patients with affective psychosis were divided into three diagnostic groups: unipolar (DJ, n = 54) and bipolar (DD, n = 20) endogenous depressions and non-endogenous depression (DN, n = 10). The control group (GK, n = 25) consisted of mentally healthy people. Hormone tests TRH and ITT were performed before and after the treatment. The hormones: TSH, T4, T3, PRL, GH, and CORT were marked by RIA methods. The findings of the examination, after being statistically described and thoroughly discussed, show that they could be useful in differential diagnosis of affective illnesses and in prognosis of therapeutic response.
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PMID:[Psychopathologic picture of depression and the conduct of some hormone tests and the therapeutic response to thymoleptics]. 129

Biological tests may help clarify the relationship of schizoaffective disorder to major depressive disorder (MDD) and schizophrenia (SCZ). Thyrotropin-releasing hormone (TRH), 500 micrograms, was administered intravenously to eight schizoaffective depressed (SD), ten SCZ, 23 MDD patients and 43 healthy controls (HC), all males, ages 20-66 years and drug-free. Research Diagnostic Criteria (RDC) were utilized for establishing diagnoses, Hamilton Rating Scale for Depression (HRSD) total scores were used for assessing depressive symptoms. There were no differences in dmax PRL (post-TRH prolactin peak minus baseline, mean +/- SD) amongst SD, SCZ and HC groups (27.3 +/- 5.2, 28.8 +/- 5.4 and 31.5 +/- 5.6 ng/ml respectively). Mean dmax PRL in MDD was significantly lower than each of the other three groups (17.1 +/- 2.2 ng/ml, P less than 0.05 for all). The essentially normal PRL response to TRH in SD, significantly different from MDD but similar to SCZ parallels our previous observations on the pattern of thyrotropin (TSH) response to TRH in the same diagnostic groups. These biological findings may be taken to indicate that schizoaffective disorder, depressed subtype, is closer to schizophrenia than to major depressive disorder. However, they cannot be considered definitive evidence to that effect since schizoaffective disorders are known to be quite heterogeneous, and since the utilized biological tests lack specificity.
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PMID:Prolactin response to thyrotropin-releasing hormone in schizoaffective depressed compared to depressed and schizophrenic men and healthy controls. 212 54

To investigate central neurotransmitter function in depression, baseline levels of serum cortisol and prolactin and the responses of these hormones to the putative serotonin agonist fenfluramine (60 mg, oral) were examined in 27 depressed patients and 14 normal subjects. Baseline cortisol was significantly elevated (P less than 0.01) in depressed subjects, whilst baseline prolactin was significantly reduced (P = 0.01) after covarying for cortisol. Although there were no significant abnormalities in either the prolactin or the cortisol response to fenfluramine in the total depressed group, the peak increase in prolactin levels (delta PRL) was significantly reduced (P less than 0.05) in subjects with endogenous depression. Analysis of covariance demonstrated, however, that the reduced delta PRL was partially dependent upon the abnormal baseline prolactin and cortisol levels. These results indicate the necessity of accounting for these baseline effects when investigating hormonal responses to the putative serotonergic challenges. The abnormal baseline findings are consistent with increased central noradrenergic activity in depression.
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PMID:Hormonal responses to fenfluramine in depressed and control subjects. 214 Aug 46

The effects of dopamine (DA) on voltage-dependent Ca2+ currents were investigated in cultured rat lactotroph cells using the patch clamp recording technique. Each recorded cell was identified by the reverse hemolytic plaque assay. In the whole-cell configuration, two types of Ca2+ currents, L and T, were characterized on the basis of their kinetics, voltage sensitivity, and pharmacology. The L component had a threshold of -25 mV, showed little inactivation during a 150-msec voltage step, and was maximal at +10 mV. Cadmium ions (100 microM) significantly reduced its amplitude (75%). The T component was activated at a membrane potential close to -50 mV, was maximal at -10 mV, and showed a voltage-dependent inactivation between -90 and -30 mV. It was quickly inactivated during a maintained depolarization (time constant, 27 ms at -30 mV) and was strongly reduced (80%) by nickel ions (100 microM). Bath application of DA (10 nM) caused a markedly general depression of inward Ca2+ currents, acting differently on the T- and L-type currents. DA application shifted the voltage-dependence of the L-type current activation toward depolarization values (8 mV) without modifying its time- and voltage-dependent inactivation. In contrast, DA enhanced the inactivation of the T-type current by accelerating its time-dependent inactivation (25% decrease in the time constant of inactivation) and by shifting the voltage-dependence of the T-type current inactivation toward hyperpolarizing values (-63 mV in control vs. -77 mV in the presence of DA). These effects of DA were dose-dependent and involved the activation of a D2 receptor type. They were mimicked by bromocriptine application (10 nM), whereas sulpiride (100 nM) blocked the DA-evoked response. The D1 antagonist SCH 23390 was ineffective up to 100 microM. All of these DA-induced modifications in Ca2+ currents were abolished using a GTP-free pipette solution or after pretreatment of cells with pertussis toxin, suggesting that DA can regulate the function of Ca2+ channels through GTP-binding proteins (G-proteins). Our results show that DA acts simultaneously by reducing both voltage-dependent Ca2+ currents on lactotroph cells. Thus, DA reduces the entry of Ca2+ ions across the surface membrane and thereby influences electrical activity and the cytosolic free Ca2+ concentration involved in both basal and evoked PRL release.
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PMID:Dopamine inhibits two characterized voltage-dependent calcium currents in identified rat lactotroph cells. 216 20

Recent reports of altered TSH responsiveness to its releasing hormone (TRH) in women with premenstrual syndrome (PMS) suggested that subclinical hypothyroidism may be responsible for the mood changes, such as depression, that occur in these women. In this study we measured basal and TRH-stimulated serum TSH and PRL levels in 15 women with PMS and in 19 age-matched normal women. The mean baseline serum TSH concentrations were similar in the 2 groups in both the follicular [normal, 1.3 +/- 0.2 (+/- SE); PMS, 0.9 +/- 0.2 mU/L] and luteal (normal, 1.1 +/- 0.2; PMS, 1.1 +/- 0.2 mU/L) phases of the cycle. The mean baseline serum PRL levels also were similar in the 2 groups in the follicular (normal, 16 +/- 2; PMS, 13 +/- 2 micrograms/L) and luteal (normal, 13 +/- 2; PMS, 14 +/- 2 micrograms/L) phases of the cycle. After TRH administration, peak serum PRL and TSH levels were reached at 15 and 30 min, respectively, and the response curves were virtually identical in the 2 groups in both phases of the cycle. One normal woman had elevated basal and TRH-stimulated TSH concentrations compatible with subclinical hypothyroidism, but had normal noncyclic scores on her prospective rating scales. Our findings suggest that PMS is not associated with thyroid dysfunction or abnormal PRL secretion and that thyroid hormone replacement therapy is not indicated in this condition.
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PMID:Thyrotropin and prolactin responses to thyrotropin-releasing hormone in premenstrual syndrome. 249 39

The object of this study was to compare the effects of short photoperiod (SP) and melatonin (MEL) treatment on the reproductive axis in ovariectomized LSH/SsLak hamsters. Animals acclimatized in long photoperiods (LP) (14L:10D) and showing regular estrous cycles were ovariectomized. Half of the operated hamsters received Silastic capsules containing 17-beta estradiol (E2). On the following day the animals were further subdivided into three groups: the animals in one group received daily afternoon injects of melatonin (MEL), those in a second group were given the vehicle, and animals in the third group were transferred from LP to SP (8L:16D). All animals were killed after 30 days. In hamsters without E2 replacement, MEL or SP exposure significantly suppressed serum and pituitary FSH levels, although MEL was more effective in this regard. On the other hand, SP exposure did not change serum FSH levels in animals with E2 implants, whereas MEL effectively suppressed them. SP or MEL reduced serum LH levels to a similar extent in the absence of E2 replacement, yet in animals with E2 implants only MEL significantly lowered LH levels below LP E2-treated controls. This was in contrast to effects on the pituitary where both treatments were equally effective in the depression of LH content. Serum PRL levels were similarly suppressed by MEL or SP exposure in E2-treated hamsters. On the other hand, pituitary PRL levels were not affected by either treatment in animals with E2-containing capsules, whereas SP or MEL treatment both significantly depressed pituitary PRL contents in hamsters without E2 replacement. SP treatment lowered MBH LHRH contents in animals with E2-containing capsules; no other significant changes in hypothalamic LHRH were noted. The data suggest that daily treatment with 25 micrograms of MEL is generally more effective in the suppression of gonadotropin levels than SP exposure. It is suspected that the mode of administration of MEL, and its quantity, may interact with estrogen differently than SP in the induction of physiological changes and regulation of the LHRH system.
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PMID:Comparison of the effects of short photoperiod exposure and melatonin treatment in ovariectomized LSH/SsLaK hamsters. 250 75

We recently reported that acute pharmacologic depression of dopaminergic tone at different times of day unmasks a sex-specific endogenous stimulatory rhythm regulating PRL secretion. The PRL secretory responses of ovariectomized rats to the dopamine antagonist domperidone (DOM) were higher at 0300 and 1700 h than at 1200 h. These are the times during which surges of PRL appear in mated rats. This experimental paradigm was used to investigate the roles of the putative PRL-releasing factors (PRFs) oxytocin (OT), vasoactive intestinal peptide (VIP), and serotonin (5-HT) in this rhythm. The role of OT was studied by infusion of the OT antagonist 1-deamino-2-D-Trp-4-Val-8-Orn-Oxytocin (OT-A, 0.5 microgram/kg min) for 6 h. Two hours after beginning the OT-A infusion DOM was administered, as a single injection of 200 micrograms/kg iv at either 0300, 1200, or 1700 h. Serial blood samples were collected immediately before and 5, 10, 20, 30, 60, 120, 180, and 240 min after DOM administration. Infusion of OT-A attenuated the heightened PRL secretory responses to DOM given at both 0300 and 1700 h but did not affect the response at 1200 h. The role of VIP was studied by infusing the VIP antagonist [D, 4-Cl-Phe6,Leu17] VIP (VIP-A, 0.1 microgram/kg.min) as described above. VIP-A infusion had no effect on the PRL secretory responses to DOM given at 1200 or 1700 h but attenuated the heightened response at 0300 h. In order to study the role of 5-HT in the rhythm, rats were pretreated with p-chlorophenylalanine (250 mg/kg sc) 48 and again 24 h before the experiment. Pretreatment with p-chlorophenylalanine had no effect on the PRL secretory responses to DOM given at 0300 or 1200 h, but it attenuated the augmented PRL secretory response at 1700 h. These data suggest that both VIP and OT act as endogenous PRFs at 0300 h and 5-HT and OT act as PRFs at 1700 h. We propose that VIP and 5-HT are continuously active oscillatory neurotransmitters regulating OT release into pituitary portal blood and that these daily events only eventuate in PRL release when the mating stimulus has release the lactotroph from the inhibitory effects of dopamine.
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PMID:Hypothalamic factors involved in the endogenous stimulatory rhythm regulating prolactin secretion. 252 68

In the rat, PRL secretion is under inhibitory control by tuberoinfundibular dopaminergic neurons. The levels of dopamine (DA) in hypophysial portal blood decline during surges of PRL secretion (e.g. suckling and cervical stimulation). However, this decline alone is not sufficient to account for the amount of PRL released. In this study we investigated the possible existence of an endogenous stimulatory rhythm for PRL secretion that may be masked by the tonic inhibitory tone of DA and unmasked by the DA-lowering effects of cervical stimulation. The PRL secretory response to pharmacological depression of DA-ergic tone was studied in ovariectomized (OVX) female, adult castrated (AC) male, neonatally androgen-sterilized (TP) female, and neonatally castrated (NC) male rats. Since mated rats have serum PRL surges at 0300 and 1700 h, these groups were treated with 200 micrograms/kg domperidone (DOM), iv, at 0300 h, 1700 h, or the intersurge interval, 1200 h. Serial blood samples were collected immediately before and at frequent intervals after DOM injection. OVX female rats had significantly greater serum PRL responses to DOM at 0300 and 1700 h than at 1200 h. AC male rats secreted significantly less PRL in response to DOM compared to OVX rats, and their PRL responses to DOM were similar at all three times. TP female rats had PRL secretory responses similar to those of the OVX rats at 1200 h, and the responses at 0300 and 1700 h were similar. NC male rats had PRL secretory responses similar to those of AC male rats. There was no difference between the PRL secretory profiles at any time after DOM injection in NC rats. These data provide evidence for an endogenous stimulatory rhythm for PRL secretion that is specific to female rats. They further suggest that the neonatal steroid environment is critical for differentiation of some sexually specific characteristics.
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PMID:A sex-specific endogenous stimulatory rhythm regulating prolactin secretion. 290 62


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