Effect of fenfluramine on growth hormone and prolactin secretion in obese subjects

Obese subjects show a subnormal growth hormone (GH) and prolactin (PRL) release in response to a variety of stimuli. Fenfluramine, an anorexiant drug used in obesity therapy, may have some effects on hypothalamic-pituitary function mediated by serotoninergic stimulation. The present investigation in obese subjects was carried out to study the effects of fenfluramine (60 mg orally) on GH and PRL secretion after intravenous arginine infusion. Ten volunteer obese females were studied and compared with 10 volunteer normal weight controls. In the obese group the GH response to arginine was significantly lower than in control group. Fenfluramine administration restored the subnormal GH response to arginine in obese subjects. The PRL response to arginine in obese women was subnormal. Fenfluramine administration restored the response of PRL to arginine infusion to normal. In conclusion, fenfluramine--under acute circumstances--enhances the hypothalamic-pituitary response to arginine in obese subjects. The decreased GH and PRL output in obese subjects is not due to an absolute hormonal deficiency and this effect of fenfluramine on GH secretion may--due to its lipolysis stimulation--be useful in obesity treatment.     

Effect of bromazepam on growth hormone and prolactin secretion in normal subjects

The growth hormone and prolactin response to oral bromazepam (3 mg) was assessed in 5 normal men and 5 normal women. A peak growth hormone response of 11.9 +/- 3.7 ng/ml (mean +/- SD), significantly above the baseline (p less than 0.01), was achieved in the men. On the other hand, there was no statistically significant response of growth hormone secretion in the women. No change in prolactin secretion was observed in either sex.     

Effect of glucagon on growth hormone secretion in rats

Gentled rats injected subcutaneously with glucagon (20 microgram/100 g body weight) showed a significant decrease in plasma growth hormone (GH) at 15 min after glucagon injection. A subcutaneous injection of 50% glucose did not cause the early suppression as shown at 15 min after glucagon injection, but at 30 min after glucose injection a tendency to decrease in plasma GH was observed. In urethane anesthetized rats, a subcutaneous administration of glucagon (1 microgram or 10 microgram/100 g body weight) failed to elicit an increase in plasma GH. In vitro incubation of anterior pituitary fragments with glucagon failed to decrease the release of GH, suggesting that glucagon does not act directly on the anterior pituitary.     

Suppressive effects of cholecystokinin and bombesin on growth hormone and prolactin secretion in urethane-anesthetized rats

The effects of cholecystokinin octapeptide (CCK) and bombesin on rat plasma growth hormone (GH) and prolactin (PRL) levels were investigated with the animals under urethane anesthesia. Intraventricular administration of both CCK (0.3 micrograms) and bombesin (2 micrograms) completely suppressed the GH secretion induced by FK 33-824, chlorpromazine (CPZ) or prostaglandin E2(PGE2). Both peptides also completely suppressed the PRL secretion induced by FK 33-824 or PGE2, and partially that induced by CPZ, but not that induced by domperidone. The intravenous administrations of CCK and bombesin had no or lesser potency in inhibiting the stimulated GH or PRL releases. These results indicate that the CCK and bombesin act much in the same manner to inhibit GH and PRL. These peptides may suppress the GH and PRL secretions via a hypothalamus-related action.     

Effect of sustained hyperglycemia on growth hormone secretion in free-moving rats

Sustained hyperglycemia was shown not to suppress growth hormone secretion in the free-moving conscious rat. It is concluded that the rat is not a suitable model for the study of the effects of glucose on growth hormone secretion.     

Inhibition of prolactin and growth hormone secretion by nickel

Nickel (Ni++) is a potent inhibitor of prolactin (PRL) secretion from isolated rat pituitary quarters in vitro, suppressing both basal PRL release and the stimulation of PRL secretion due to theophylline and dibutyryl cyclic AMP. Stimulation of growth hormone (GH) secretion by synthetic GHRH is also blunted by Ni++, although basal GH release and stimulated GH release due to theophylline or dibutyryl cyclic AMP are not suppressed. Ni++ antagonizes the stimulation of both PRL and GH secretion by barium (Ba++) ion, suggesting that the inhibitory effects of Ni++ on hormone release are due to an antagonism of calcium uptake or redistribution.     

Thyroid stimulating hormone and prolactin secretion: reduced sensitivity to TRH-stimulated prolactin release after midpregnancy in rats

Prolactin (PRL) and thyroid stimulating hormone (TSH) plasma concentrations were measured during the latter part of the dark period in early and mid-late pregnancy in the rat. On Days 4-5 and 7-8 of pregnancy, plasma PRL concentrations surged between 22:00 and 06:00 hr and TSH values increased between 22:00 and 02:00 hr. While the TSH pattern was maintained during the second-half of pregnancy, surges in PRL release ceased and PRL levels remained at less than 10 ng/ml. The effects of thyrotropin releasing hormone (TRH) administration on PRL and TSH secretion were then measured to determine whether the second-half of pregnancy is associated with a decrease in sensitivity to an agent that can stimulate PRL release. Injection (iv) of cannulated pregnant rats with a low dosage (20 ng) of TRH stimulated a twofold increase in plasma TSH during both early (Days 5-9) and later (Days 14-18) pregnancy but did not change plasma PRL levels. Treatment with a high dosage (2 micrograms) of TRH induced a sixfold rise in plasma TSH during both phases of gestation. The higher dose of TRH also stimulated elevations in plasma PRL during early and mid-late pregnancy; however, both the absolute increase in the amount of PRL in plasma and the percentage increase over baseline levels were greater from Days 5-9 than from Days 14-16 of gestation. These data indicate that the neuroendocrine sensitivity to factors that stimulate PRL secretion changes as pregnancy progresses, and suggest that nocturnal secretion of PRL and TSH during pregnancy may be regulated, in part, by a common trophic factor.     

Differences in growth hormone and prolactin secretion associated with environmental temperature and energy intake

The combined effects of environmental temperature and level of energy intake on plasma concentrations of growth hormone (GH) and prolactin (PRL) have been investigated in 14 week old pigs acclimated to 35 or 10 degrees C on a high (H) or low (L) energy intake (H = 2L). Measurements were made at 15 min intervals between 08.00 and 18.00 hours, after feeding at 17.00 hours on the previous day. Mean values of GH were greater in pigs on the L than H intake and there was a tendency for values to be higher at 35 than 10 degrees C. However, there was wide individual variation within each treatment group and the differences were not statistically significant. Mean PRL concentrations were greater at 35 than 10 degrees C (P less than 0.05). It is concluded that circulating levels of plasma GH do not have a major role in maintaining the differences in growth and morphology of young pigs kept in widely different environmental conditions. However, these differences could be related at least in part to the GH-like properties of PRL.     

Prenatal androgen exposure and growth and secretion of growth hormone and prolactin in ewes postweaning

Growth and secretion of growth hormone (GH) and prolactin (PRL) in ewe lambs exposed to androgen during fetal development were investigated. Testosterone cypionate was administered to the pregnant dams from approximately Days 28 to 84 of gestation. Ewe lambs from dams that received androgen exhibited masculinized external genitalia and some masculine behavioral characteristics. Intact androgenized ewe lambs grew faster (P less than 0.05) and were more efficient in conversion of food to body gain (P less than 0.05) than ewe lambs born to untreated dams over the period from 70 to 224 days of age. One-half of the ewe lambs in each group was ovariectomized at 58 days of age. Ovariectomy had no effect on subsequent growth or efficiency of growth in the control ewe lambs. However, ovariectomy of androgenized ewe lambs abolished the observed stimulated rate of growth and decreased the improvement in efficiency of food conversion. Blood samples were collected from the lambs at 85 and 136 days of age at 15-min intervals for 8 hr to determine parameters of GH and PRL secretion. Prenatal androgen exposure had no effect on any parameter of GH or PRL secretion. These data indicate that prenatal androgen exposure altered differentiation of growth potential in ewe lambs, but the growth response was not mediated through dramatic changes in secretion of adenohypophysial somatotropic hormones, GH and PRL.     

Serotoninergic drugs affect prolactin and growth hormone secretion in the domestic fowl

Adult fowl of both sexes injected with the monoamine oxidase inhibitor pargyline showed elevated circulating prolactin concentrations and reduced growth hormone concentrations. Young cockerels injected with the serotonin agonist quipazine and the antagonist methysergide showed responses consistent with a serotoninergic stimulatory control of prolactin. Injection of the serotonin precursor tryptophan and the serotonin re-uptake blocker imipramine resulted in elevated prolactin and reduced growth hormone levels. The similarities and differences in the control of prolactin and growth hormone in birds and mammals were discussed.     

Effect of opioid agonist-antagonist interaction on morphine dependence in rats

Morphine dependence was induced by treatment with morphine-admixed food (0.25mg/g of food) for 7 days. Withdrawal was precipitated by injecting naloxone (0.5mg/kg, s.c.). Rats treated with morphine exhibited body weight loss upon the naloxone injection. When morphine-dependent rats were injected subcutaneously with morphine, codeine, meperidine and pentazocine 30 min before the naloxone injection, these drugs significantly suppressed the naloxone-precipitated loss of body weight in a dose-dependent manner. However, body weight loss induced through coadministration of naloxone and Mr-2266 BS were not suppressed by morphine pretreatment. These results suggest that opioids protect against naloxone-precipitated loss of body weight, and that mu and kappa opiate receptors play an important role in the protection against naloxone-precipitated withdrawal.     

Effect of adrenergic antagonism on the growth hormone, prolactin and cortisol response to a synthetic opioid agonist in man

The intravenous administration of 250 micrograms D-Ala2-MePhe4-Met-enkephalin-O-ol (DAMME) caused a marked increase in circulating growth hormone (GH) and prolactin (PRL), and a fall in cortisol, in 14 normal subjects. Neither the alpha 1-antagonist thymoxamine, nor the alpha 2-antagonist yohimbine, significantly altered the GH and PRL responses to DAMME, suggesting that in man the growth hormone- and prolactin-releasing effects of exogenous opioids are not mediated through adrenoceptor pathways. The fall in cortisol induced by DAMME was not affected by thymoxamine, but was significantly attenuated by yohimbine, indicating that opioids may lower circulating cortisol via an interaction with noradrenergic pathways.     

The effects of opiate agonists on growth hormone and prolactin release in rats

Various opioid receptor agonists, including Met5-enkephalin amide, Leu5-enkephalin amide, [D-Ala]2-Met5-enkephalin amide, [D-Ala]2-Leu5-enkephalin amide, morphine sulfate, d-methadone hydrochloride, and l-methadone hydrochloride were administered to adult male rats by subcutaneous injection. All opioid receptor agonists except Leu5-enkephalin amide significantly stimulated growth hormone and prolactin release. Naloxone and naltrexone blocked the hormone stimulatory effects of the opioids and both naloxone and naltrexone, when administered alone, significantly reduced serum growth hormone and prolactin concentrations. The dopaminergic agonist apomorphine, but not the alpha-adrenergic agonist clonidine, blocked opiate stimulation of prolactin. Morphine sulfate caused growth hormone release in rats pretreated with alpha-methyl-p-tryosine, a catecholamine synthesis inhibitor. Cholinergic agonists, physostigmine and pilocarpine, antagonized the growth hormone and prolactin release induced by morphine sulfate. The data suggest that the opiates stimulate prolactin via an interaction with catecholaminergic neurons controlling prolactin release and stimulate growth hormone via a mechanism independent of alpha-adrenergic or general catecholaminergic influence. The mechanism through which cholinergic agonists act to inhibit opiate agonist stimulation of growth hormone is presently unknown.     

Effect of prolactin and growth hormone on prolactin and LH receptors in the dwarf mouse.

Dwarf mice (DW/J;dw/dw) which exhibit a deficiency of prolactin and GH secretion were treated for 8 days with ovine prolactin and/or human GH (10 or 20 mug/day) and the effect on hepatic and testicular prolactin receptors was investigated. In both sexes there was a significant increase in body weight after all hormone treatments, but an increment in testicular weight was observed only after prolactin administration. Prolactin treatment increased the specific binding % of prolactin in liver membranes in females but not males, and in testicular homogenates (together with an increase in LH receptors). The results suggest that lack of prolactin but not of GH retards sexual development in these mice. Treatment with prolactin partly counteracts this deficiency, and the effect may be mediated by the induction of hepatic and testicular prolactin and LH receptors.