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Biomedical subjects

A Grossman

Publications and source records attributed to A Grossman.

At least 271 records · Page 15Linked to original sources
PubMed1983

The participation of hypothalamic dopamine in morphine-induced prolactin release in man.

In order to assess the role of dopamine in opiate-induced prolactin secretion, morphine alone or in combination with the dopamine blocker metoclopramide, or the L-aromatic aminoacid decarboxylase inhibitor benserazide, was administered to a group of normal adult men. Morphine (10 mg) stimulated prolactin release in all subjects; however, the effect was totally abolished when 10 mag metoclopramide or 200 mg benserazide were given before the opiate agonist. The prolactin releasing effect of a sub-maximal metoclopramide dose (1 mg) was potentiated by morphine. In vitro, benserazide was totally inactive in stimulating prolactin release by isolated anterior pituitary cells. Moreover, benserazide failed to alter the inhibiting action of dopamine on prolactin release. The data suggest that opiates stimulate prolactin release in man by acting through dopaminergic mechanisms.

Adult↗
PubMed1983

Opiate peptides control growth hormone through a cholinergic mechanism in man.

Opiate peptides are known to elevate circulating GH in man, and data in other animals suggest that acetylcholine may be involved. We have administered the long-acting met-enkephalin analogue DAMME to 6 normal males, and have shown that the resulting elevation in GH is blocked by the specific cholinergic antagonist, pirenzepine. It seems likely that a cholinergic mechanism may interact with opiate-induced changes in GH in man.

Adult↗
PubMed1983

Naloxone inhibits exercise-induced release of PRL and GH in athletes.

Opiate peptides stimulate the release of GH and PRL, and such changes have also been reported following physical exercise. To investigate opiate involvement in the exercise-induced release of these hormones, eight professional athletes were exercised to 80% of their maximal heart rate on a bicycle ergometer. This exercise alone induced an increase in circulating mean GH (basal to maximal level, 3.1 +/- 0.9 ng/ml-27.3 +/- 5.9 ng/ml) and mean PRL level (6.1 +/- 1.1 ng/ml-19.5 +/- 1.9 ng/ml). Infusion of naloxone (0.3 mg/min) antagonized these responses in mean serum GH (5.6 +/- 1.0 ng/ml to 8.6 +/- 1.1 ng/ml) and PRL levels (6.4 +/- 1.1 ng/ml-8.1 +/- 1.2 ng/ml), which were both significantly less than during the control infusions (P less than 0.01). It is suggested that certain forms of stress stimulate the release of PRL and GH via endogenous opiate peptides.

Adult↗
PubMed1983

Pro-opiocortin related peptides in human pituitary and ectopic ACTH secreting tumours.

Basal and stimulated secretion of N-terminal pro-opiocortin (Pro-gamma-MSH), ACTH and LPH from seven pituitary and three ectopic ACTH secreting tumours have been studied in vitro using a perfused isolated cell system. The peptides were shown to be released concomitantly and in equimolar amounts. The pituitary tumours responded to stimulation with rat stalk median eminence extracts (SME) and synthetic AVP. However, peptide release from the ectopic tumours, although pulsatile, remained autonomous. Prior to surgery, gel-chromatographic profiles of plasma immunoreactive ACTH showed only one peak, which eluted in the position of 1-39 ACTH, in patients with the pituitary tumours, but there was a second peak of large molecular weight ACTH present in the plasma from those with the ectopic ACTH syndrome. This second form of ACTH could not be detected in any of the tumour cell column effluents. An eighth pituitary tumour was atypical, in its unusually large size, clinically aggressive nature and spectrum of peptide release. Although peptide release in response to stimulation with SME was similar to that observed with the other pituitary tumours, the chromatography of the plasma ACTH resembled the ectopic plasma pattern, showing two peaks of immunoreactivity.

ACTH Syndrome, Ectopic↗
PubMed1983

Dopaminergic control of the rat thyrotroph.

The established technique of dynamic perfusion of dispersed rat anterior pituitary cells was used to investigate the role of dopamine in the release of thyroid-stimulating hormone (TSH). The basal release of TSH was 124 +/- 22 ng/ml (mean +/- SEM) and this remained unchanged in the presence of dopamine (5 X 10(-6) M), while basal prolactin release was suppressed to 50% of control values. Perfusion with thyrotrophin-releasing hormone (TRH) in doses between 1.4 X 10(-10) and 22.4 X 10(-10) M produced a consistent and reproducible dose-response curve for TSH (n = 14) which was not significantly altered by the presence of dopamine (n = 5). Perfusion with bromocriptine (10(-6) M), a dopamine agonist, did not alter the basal or stimulated TSH release. No stimulation of TSH release was observed when the cells were challenged with 2-min pulses of domperidone, a dopamine antagonist (2 X 10(-9) to 2 X 10(-5) M). The inclusion of somatostatin-14 (3 X 10(-9) M) in the perfusate inhibited TRH-stimulated TSH release. Our results suggest that, in the rat, dopaminergic inhibition of TSH release does not occur at the level of the pituitary.

Animals↗
PubMed1983

Differential effects of opiate peptides and alkaloids on anterior pituitary hormone secretion.

In order to investigate the opiate receptors involved in the control of anterior pituitary hormone secretion, five different opioid drugs were administered intravenously to groups of 6 normal male subjects. Morphine (10 mg), methadone (10 mg), pentazocine (30 mg), nalorphine (10 mg) and 0.25 mg of the met-enkephalin analogue, DAMME, all caused similar increases in circulating prolactin with falls in serum LH and cortisol. Methadone and DAMME also elevated GH and TSH; morphine elevated TSH but not GH, nalorphine GH but not TSH. After pentazocine neither GH nor TSH changed. FSH failed to change significantly after any drug. All these changes, except serum cortisol, were antagonised by 4 mg naloxone. Taking into account the known receptor subtypes preferentially activated by each opiate, it is suggested that prolactin secretion is modulated by epsilon-receptors and TSH by mu-receptors. The control of ACTH probably involves delta-or kappa-receptors, that for LH kappa-or epsilon-receptors. It is not possible on present data to allocate a specific receptor mediating the opioid control of GH.

Adult↗
PubMed1983

Analysis of binding of [3H]Estradiol to the cytosol fraction of rat pancreas: comparison with sites in the cytosol of uterus.

The cytosol fraction of rat pancreas [100,000 X g (for 1 h) supernatant] demonstrated specific but nonsaturable binding of [3H]estradiol in the concentration range of 2-50 X 10(-9) M. Scatchard analysis of specifically bound [3H]estradiol, determined by the isotope dilution technique (competition with excess unlabeled estradiol), indicated a single class of binding sites (approximately 4.4 pmol/mg protein) with an apparent Kd of 5 X 10(-8) M. Such cytosol fractions, prepared from homogenates that contained protease inhibitors, when prelabeled with [3H]estradiol, demonstrated a single sharp eluate peak of radioactivity after Sephadex G-200 chromatography that corresponded to a molecular weight of 120,000. When protease inhibitors were omitted, [3H]estradiol was associated with material of considerably lower molecular weight. Routinely, the protease inhibitors leupeptin (1 mM), phenylsulfonyl fluoride (0.5 mM), and tosylphenylalanylchloromethyl ketone (0.05 mM) were included in the buffer used for homogenizing both the pancreas and uterus. The protein that binds [3H]estradiol in uterus differed from that in pancreas in a number of ways: 1) in the range of 10-20 X 10(-9) M [3H]estradiol, specific binding of the hormone to uterine sites was saturable, and Scatchard analysis indicated a single class of binding sites, (approximately 0.5 pmol/mg protein) having an apparent Kd of 3 X 10(-10) M; 2) the rate constants of dissociation of the [3H] estradiol-bound complexes in pancreas and uterus were 3.1 X 10(-4) sec-1 (t1/2, 37 min) and 8.7 X 10(-5) sec-1 (t1/2, 134 min), respectively; 3) the molecular weight of the estrogen-binding protein in freshly prepared uterine supernatant fractions appeared to be at least 240,000; this was unaltered regardless of whether protease inhibitors were present during initial homogenization of the tissue; and 4) when uterine supernatants prepared in the absence of protease inhibitors were kept at 8 C for 24 h and then analyzed by Sephadex G-200 chromatography, a second peak of [3H]estradiol-binding activity appeared at the same eluate volume as the low molecular weight binding fractions of pancreas. These data suggest that although the binding proteins in pancreas and uterus are different, there may be some common features at the hormone-binding locus.

Animals↗
PubMed1982

The role of opiate peptides in the control of prolactin in the puerperium, and TSH in primary hypothyroidism.

The role of endogenous opiate peptides in puerperal hyperprolactinaemia, and in the control of TSH in hypothyroidism, has been investigated. Although exogenous opioids raise prolactin and TSH levels, 16 mg naloxone administered to women on days 2-4 of the puerperium produced no significant change in serum prolactin and the same dose of naloxone had no significant effect on serum TSH in six primary hypothyroid patients. There is little evidence that endogenous opioid peptides are major modulators of prolactin or TSH in man under these conditions.

Endorphins↗
PubMed1982

Opiate modulation of the pituitary-adrenal axis: effects of stress and circadian rhythm.

The opiate control of the pituitary-adrenal axis has been investigated in normal subjects. The infusion of 1 mg of the met-enkephalin analogue, DAMME, led to a fall in circulating cortisol in spite of a fall in blood pressure. Conversley, 16 mg of the opiate antagonist, naloxone led to brisk and pronounced elevations in plasma ACTH, lipotrophin (LPH) and cortisol. The rise above basal levels was consistent, irrespective of whether the infusion was given at 09.00, 18.00, or 23.00 h; the peak response obtained was significantly less at 23.00 h than at either 09.00 or 18.00 h. Finally, insulin-induced hypoglycaemia (0.15 u/kg) or naloxone (25 mg) produced a similar rise in plasma cortisol which was no different when the two stimuli were combined. It is suggested that there is a constant tonic inhibition of the pituitary-adrenal axis by endogenous opiates throughout 24 h, and that the circadian rhythm of ACTH/LPH secretion is not due to changes in opiate tone. However, disinhibition of this tone is likely to be responsible, at least in part, for the rise in cortisol in response to hypoglycaemic stress.

Adolescent↗
PubMed1982

Opiate mediation of amenorrhoea in hyperprolactinaemia and in weight-loss related amenorrhoea.

Endogenous opiates are involved in the control of pituitary gonadotrophin and PRL secretion, and possibly of food intake. Both hyperprolactinaemia and weight loss (especially in anorexia nervosa) are frequently associated with amenorrhoea and an absence of gonadotrophin pulsatility. Since it has been suggested that increased endogenous opiate tone may operate in both conditions, we infused high-doses of naloxone into twelve patients with amenorrhoea of whom five had hyperprolactinaemia and seven had weight-loss related amenorrhoea. Eleven of the twelve patients had low levels of oestradiol (less than 50 pmol/l). Naloxone induced a marked rise in both LH and FSH levels in all of the five hyperprolactinaemic patients. In contrast, the patients with weight-loss amenorrhoea responded to naloxone with only a small or no rise in gonadotrophins. There was no consistent change in PRL in either group of patients. It is concluded that in hyperprolactinaemia, but not weight-loss amenorrhoea, there is an important endogenous opiate-mediated tonic inhibition of secretion of hypothalamic gonadotrophin releasing hormone.

Adolescent↗
PubMed1981

Requirement for an accessory factor for binding of [3H]estradiol to protein in the cytosol fraction of rat pancreas.

Supernatant fractions from rat pancreas bind approximately 300 fmol of [3H]estradiol per mg of protein when incubated with 5 nM [3H]estradiol for 1 hr at room temperature. Passage through gel filtration columns reduces binding in the eluate to approximately 1% of its initial activity. Extracts of the supernatant contain a factor that reactivates binding in gel filtrates. Addition of accessory factor to fractional eluates gives one sharp peak of activity. Since fractions that cannot be reactivated contain as much or more protein as fractions that can be reactivated, it is concluded that interaction of accessory factor and [3H]estradiol-binding protein is specific. Peptides such as antipain [(1-carboxy-2-phenylethyl)carbamoyl-L-arginyl-L-valyl-L-argininal] and, especially, N-benzoyl-L-phenylalanyl-L-valyl-L-arginine-p-nitroanilide also enhanced binding of [3H]estradiol. Accessory factor is water soluble, dialyzable, and heat stable. Although as currently purified, it contains several substances, the data suggest that at least one component of accessory factor is an oligopeptide.

Animals↗
PubMed1981

The effect of naloxone on pulsatile gonadotrophin release in normal subjects.

The gonadotrophin response to naloxone infusion has been investigated in three adult males, and three adult females in the early follicular phase. The frequency of LH secretory episodes and the mean LH levels increased in both sexes. The data suggest that the pulsatile release of LH is under inhibitory opiate control.

Adult↗
PubMed1981

The opioid control of LH and FSH release: effects of a met-enkephalin analogue and naloxone.

The effect of long-acting analogue of met-enkephalin (DAMME) and naloxone on gonadotrophin secretion has been investigated in man. In menopausal women DAMME induced a progressive fall in LH to approximately 60% of basal levels at 3 h, which was blocked by naloxone; there was a smaller fall in FSH that did not attain statistical significance. However, the LHRH-induced rise in LH and FSH in young male volunteers was unaffected by pretreatment with a high-dose DAMME infusion. Naloxone infusion in young male and female normal subjects produced a significant rise in both LH and FSH. Long-term infusion of naloxone appeared to increase the rate, and possibly the amplitude, of LH pulsatility. These results suggest that met-enkephalin-like opioid peptides exert a tonic inhibitory control of LH release in both menopausal and young subjects of both sexes. This control is most likely to be at the level of the hypothalamus, and involves modulation of pulsatile LHRH release.

Adolescent↗