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Biomedical subjects

H Guyda

Publications and source records attributed to H Guyda.

At least 37 records · Page 2Linked to original sources

CCK-8 antagonizes apomorphine-induced growth hormone secretion in normal subjects.

Cholecystokinin octapeptide (CCK-8) (5 ug iv over 10 minutes) administered to normal men had no effect on basal growth hormone (GH) or prolactin secretion but significantly antagonized the GH response to the dopamine (DA) receptor agonist, apomorphine HCI (Apo) (0.5 mg sc), 30 (P less than 0.05) and 45 minutes (P less than 0.01) after Apo injection (n = 8). These results are compatible with an inhibitory effect of CCK-8 on certain DA mechanisms in the hypothalamic-pituitary axis. Whether CCK-8 affects DA function in other brain regions in man is unknown.

Adolescent↗

An autosomal dominant form of adolescent multinodular goiter.

Eighteen members of an extended pedigree have been found to have a form of euthyroid adolescent multinodular goiter. Histological examination showed multiple adenomata with areas of epithelial hyperplasia, hemorrhage, and calcification. In two subjects there were focal areas of epithelial hyperplasia reminiscent of low-grade papillary carcinoma, but capsular and vascular invasion was not found. The pattern of inheritance appeared to be autosomal dominant, with diminished penetrance in males. Although the patients were euthyroid, the likely basis for this disorder is an abnormality in thyroglobulin structure and function.

Adolescent↗

Effect of naloxone on menopausal flushes, skin temperature, and luteinizing hormone secretion.

The effect of naloxone (1.4 mg/hr for 3 hours) on subjectively experienced menopausal flushes, skin temperature, and luteinizing hormone secretion was investigated in seven women in a double-blind, saline-controlled, crossover study. Naloxone had no effect on the number of subjective flushes, episodic skin temperature elevation, luteinizing hormone pulses, variability of luteinizing hormone secretion, or total luteinizing hormone secretion. This study suggests that a naloxone-sensitive opioid mechanism is not active in modulating luteinizing hormone secretion in the postmenopausal woman and that opioid receptor blockade is not effective in altering the frequency of menopausal flushes.

Climacteric↗

Effect of normal aging on the prolactin response to graded doses of sulpiride and to arginine.

The prolactin (PRL) response to placebo, sulpiride (2.5, 5, 10 and 20 mg im) and arginine HC1 infusion (0.33G/kg) was examined in young (18-25 yrs) and old (65-75 yrs) normal men. Analysis of variance for the sulpiride data showed no significant dose x age group interaction or dose X age group X period interaction. There was, however, a significant age group X period interaction (p less than 0.05). PRL concentrations were significantly lower in the old subjects (N = 9) compared with the young (N = 9) 15 min after 2.5, 5, or 10 mg but not significantly after 20 mg sulpiride or at any other time interval. The areas under the concentration-time curves and the mean individual peak PRL concentrations were not significantly different between the two groups. The pattern of findings suggests a delayed absorption of sulpiride in the elderly rather than a change in pituitary dopamine (DA) receptor sensitivity to account for the lower PRL concentrations at 15 min. Differences in magnitude of the PRL response between the four doses of sulpiride were small and results suggest that the 2.5 mg dose is close to that required to saturate DA receptors on the lactotrophe and that the 10 and 20 mg doses are sufficient to completely block pituitary DA receptors. There was no significant age effect on arginine-induced PRL secretion (N = 11 in each group).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Effect of methyldopa on menopausal flushes, skin temperature, and luteinizing hormone secretion.

The effect of methyldopa (100 mg intravenously), the precursor of the alpha-receptor agonist alpha-methylnorepinephrine, on subjectively experienced menopausal flushes, skin temperature, and luteinizing hormone secretion was investigated in seven women in a double-blind, saline-controlled, crossover study. Subjects were monitored over a 3-hour period. Methyldopa significantly decreased the number of subjective flushes (p less than 0.05) and the number of cutaneous temperature peaks (p less than 0.05) but had no effect on the number of luteinizing hormone secretory pulses, variability of luteinizing hormone secretion, or total luteinizing hormone secretion. These studies indicate that alpha-adrenergic mechanisms (central and/or peripheral) play a role in the pathophysiology of menopausal flushes.

Climacteric↗

CCK-33 antagonizes apomorphine-induced growth hormone secretion and increases basal prolactin levels in man.

Cholecystokinin (CCK-33) (225 Ivy Dog Units intravenously) had no effect on basal growth hormone (GH) secretion but antagonized the GH response to the dopamine receptor agonist, apomorphine HCl (0.5 mg sc) (N = 7), and induced a transient increase in basal prolactin (PRL) secretion (N = 8) in normal men. These findings are similar to those described with neuroleptics and are compatible with an inhibitory effect of CCK-33, or fragments, on dopamine function in man, at least in the hypothalamic-pituitary axis. However, an inhibitory effect of CCK-33 on the release of GH and a stress-induced increase in PRL secretion cannot be excluded.

Adult↗

Receptors for insulin-like growth factors in rabbit articular and growth plate chondrocytes in culture.

Receptors for the insulin-like peptide ILAs have been identified in cultured rabbit chondrocytes. The cell-ILAs interaction is a time-dependent, reversible and saturable process. The cell-bound radioactive material appears as intact hormone. Insulin-like growth factor II (IGFII) is as potent as ILAs in competing for 125I-ILAs binding, whereas insulin-like growth factor I is somewhat less potent. Insulin does not affect ILAs binding. Our results suggest that the cultured chondrocytes possess a common receptor for the somatomedin peptides and that insulin, which is able to stimulate sulfate incorporation into proteoglycans, acts through an insulin receptor distinct from the somatomedin site. In growth plate chondrocytes the specific binding of 125I-ILAs is ten times lower than in articular cells in culture, whereas the sulfation activity of ILAs, at all concentrations studied, is 2.5-3 times lower in growth plate than in articular chondrocytes. The total binding of 125I-ILAs is higher to a particulate cell fraction than to intact cultured cells, by a factor of 10 for the growth plate cells, and by a factor of 2 for the articular cells. These findings suggest a poor accessibility of the hormone to the receptor sites of the growth plate chondrocytes in cultures, which are known to be surrounded by a thick matrix.

Animals↗

Neuroendocrine evaluation of CCK-peptides on dopaminergic function in man.

CCK-33 (225 Ivy Dog Units iv) antagonized the growth hormone response to the dopamine receptor agonist, apomorphine HCl (0.5 mg sc), and increased basal prolactin secretion in normal male volunteers. A stress mediated prolactin effect could not be excluded. CCK-8 (5 ug iv) antagonized the growth hormone response to apomorphine but had no effect on basal prolactin or plasma homovanillic acid. Ceruletide (0.3 ug/kg im) had no effect on basal prolactin or apomorphine-induced growth hormone secretion. CCK-33, CCK-8 and ceruletide had no effect on basal growth hormone secretion which suggests that they do not inhibit the release of growth hormone. These findings are compatible with an inhibitory effect of CCK-33 and CCK-8 (or fragments) on dopaminergic function in man, at least in the hypothalamic-pituitary axis and point to a simple way to study the effect of peptides on dopaminergic function in man including those which may not cross the blood brain barrier.

Adolescent↗

Preliminary results on the mental development of hypothyroid infants detected by the Quebec Screening Program.

A prospective study of the mental development of hypothyroid infants detected by the Quebec Network for Genetic Medicine began in January, 1976. The mean age at initiation of thyroid hormone therapy was 27 days. Forty-five hypothyroid infants and 37 normal control subjects were assessed at age 12 months with the Griffiths mental development test; 77 and 41, respectively, were assessed at age 18 months, and 59 and 40, respectively, at 36 months. There were no statistically significant differences in the various test scores between the two populations at age 12 months, but at age 18 and 36 months the hypothyroid infants had lower scores in hearing-speech performance scales and practical reasoning (36 months) which also decreased their global quotient. The mean scores were still above 100 and only nine were below 85. Further assessment of the influence of early therapy on mental development at age 6 years is needed before definitive statements can be made about the long-term mental development in these subjects.

Child, Preschool↗

Clonidine-induced growth hormone secretion in chronic schizophrenia.

Clonidine (0.15 mg intravenously), an alpha-adrenergic receptor agonist, was administered to 13 male chronic schizophrenics, who had been withdrawn from chronic neuroleptic therapy, and to 18 normal male controls. There was no significant difference in growth hormone (GH) response between the two groups. There was no significant correlation between duration of psychosis, duration of neuroleptic therapy or length of neuroleptic withdrawal and GH response. These results suggest that postsynaptic alpha-adrenergic receptor function in the hypothalamic-pituitary axis is unaltered in chronic schizophrenia or by prior chronic neuroleptic therapy.

Adult↗

Regulation of vitamin D metabolism in normal human pregnancy.

The increasing serum concentrations of various hormones (PTH, PRL, estrogens, and human placental lactogen) are hypothesized to regulate 1,25-dihydroxyvitamin D [1,25(OH)2D] and possibly 24,25-dihydroxyvitamin D [24,25(OH)2D] production during pregnancy. We examined the correlation between the serum levels of 1,25(OH)2D and the pregnancy-related hormones in 25 normal pregnant women, followed throughout gestation and postpartum. Maternal serum levels of 1,25(OH)2D were high during the first trimester (mean +/- SE, 74 +/- 8 pg/ml), remained high until the time of delivery (95 +/- 14 pg/ml), and then fell to almost normal levels (50 +/- 9 pg/ml) on the third postpartum day. The serum levels of 1,25(OH)2D do not correlate with the serum levels of any of the aforementioned hormones. The increase in serum 1,25(OH)2D in pregnancy has been postulated to be related to the stressed calcium homeostatic mechanisms known to occur in the mother. In twin pregnancy, this maternal calcium homeostatic mechanism(s) conceivably may be stressed to a greater extent. However, serum 1,25(OH)2D levels, measured in 27 women with a twin pregnancy in both the second and third trimesters as well as at delivery, did not differ from the levels observed in women with a singleton pregnancy. There were no significant changes in the serum levels of 24,24(OH)2D or 25-hydroxyvitamin D as pregnancy progressed. However, serum 24,25(OH)2D correlated significantly with both serum 1,25(OH)2D (r - 0.51; p less than 0.001, n = 83) and serum 25-hydroxyvitamin D (r = 0.37; P less than 0.001, n = 94). In conclusion, serum levels of 1,25(OH)2D rise early in the first trimester of pregnancy, fall acutely to normal levels soon after delivery, and are similar in singleton and twin pregnancies. The changes in the serum levels of 1,25(OH)2D do not relate to the changes in the serum levels of any of the pregnancy-related hormones.

24,25-Dihydroxyvitamin D 3↗

Hypothalamic-pituitary dopaminergic function in hepatic failure in man.

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 less than 0.004) and without (P less than 0.002) HE had an impaired GH response (peak increment less than 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 less than 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.

Alcoholism↗

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

Domperidone, a peripheral dopamine (DA) receptor blocker which poorly crosses the blood-brain barrier and which is inactive towards dopamine-sensitive adenylate cyclase, in a dose (100 micrograms/kg) sufficient to increase serum prolactin levels at least 5-fold, decreased the growth hormone (GH) response to the DA receptor agonist, apomorphine HCI (Apo) (0.5 gm 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 less than 0.005 -p less than 0.002). 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.

Adult↗

Effect of sulpiride, an atypical neuroleptic, on apomorphine-induced growth hormone secretion.

Sulpiride (100 mg IM), an atypical neuroleptic, which does not block dopamine (DA) receptors that are linked to adenylate cyclase, abolished the growth hormone (GH) response to the DA receptor agonist, apomorphine (Apo) HCl (0.5 mg SC) in seven healthy male subjects. These results suggest that Apo increases GH secretion in man by an effect on DA receptors that are not linked to adenylate cyclase.

Adult↗

Drug-induced growth hormone and prolactin responses in schizophrenia research.

1. Interpretation of neuroendocrine studies in schizophrenia requires consideration of (a) the large number of variables that affect drug-induced endocrine responses (b) the effect of prior neuroleptic therapy (c) heterogeneity of schizophrenia (d) heterogeneity of receptors (e) uniqueness of the hypothalamic-pituitary axis (f) selectivity and pharmacokinetics of administered drugs. 2. Apomorphine increases growth hormone secretion by an effect on dopamine receptors that are not linked to adenylate cyclase and which are located outside the blood brain barrier. 3. Hypothalamic-pituitary histaminergic H2 and alpha-adrenergic function are unchanged in chronic schizophrenia. 4. Schizophrenic symptoms persist despite complete blockade of dopamine receptors modulating prolactin secretion. 5. Studies on dopamine receptors modulating prolactin secretion are unlikely to shed light on the pathophysiology of schizophrenia. 6. Screening for drugs which block apomorphine-induced growth hormone secretion but do not increase prolactin may provide a way of detecting anti-schizophrenic drugs which are devoid of side effects associated with hyperprolactinemia and which do not induce parkinsonism or tardive dyskinesia.

Antipsychotic Agents↗