Comparative study of human fetal, normal adult, and somatotropic adenoma pituitary function in tissue culture.
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Biomedical subjects
Publications and source records attributed to H Guyda.
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Oral administration of choline (10 g) had no effect on basal serum growth hormone or prolactin concentrations in normal subjects (N = 5). Choline significantly enhanced the increase in growth hormone secretion induced by apomorphine HCl (0.5 mg s.c.). These data suggest that cholinergic mechanisms may enhance hypothalamic-pituitary dopaminergic function in man in contrast to their inhibitory effect on dopaminergic function in the basal ganglia.
Twenty-four hours sleep deprivation significantly decreased the growth hormone response to the dopamine receptor agonist, apomorphine HCl, in five normal men (0.5 mg s.c.) and one woman (0.75 mg s.c.) but had no effect on basal or post-apomorphine prolactin concentrations. These results suggest that sleep deprivation decreases the sensitivity of certain central dopamine receptors. The relevance of this finding to the antidepressant effect of sleep deprivation is unclear.
To determine whether old cells have a reduced response to a preparation of factors from human plasma with insulinlike activity (ILA), we analyzed the response to ILA of early and late passage human fibroblasts from young, old, and progeric donors in the acute stimulation of [3H]2-deoxy-D-glucose (2dG) uptake and the delayed stimulation of [3H]thymidine (TdR) incorporation into DNA. The ILA concentration required to produce equivalent, relative stimulation of TdR incorporation was increased two- to three-fold in late passage cells and cells from old and progeric donors (P less than 0.01). 50 and 95% of maximal stimulation (ILA50, ILA95) was achieved by 0.26 +/- 0.07 and 1.38 +/- 0.13 ng insulin equivalents/ml (mean +/- SD) respectively, in cells from young adults at early passage. Corresponding values were 0.54 +/- 0.05 and 2.90 +/- 0.25 in cells from old donors; greater than 0.9 +/- 0.1 and greater than 3.1 +/- 0.1 in cells from a 9-yr-old progeric donor; and 0.4 +/- 0.05 and 1.1 +/- 0.04 in cells from normal children (9-13 yr). For two cell strains from young adults, ILA50 and ILA95 were 0.30 +/- 0.02 and 1.0 +/- 0.3 ng eq/ml at 30% of their in vitro lifespan completed (%LC) and these values increased at rates of 0.005 ng eq/ml per %LC and 0.04 ng eq/ml per %LC, respectively. The mean stimulation of 2dG uptake ratio (ILA/control) decreased from early to late passage from 2.1 +/- 0.6 to 1.3 +/- 0.1 in young adult donors (P less than 0.05), but there were no significant differences between young and old donors at either early or late passage. The mean stimulation ratio in progeric cells (1.2 +/- 0.2) did not change with in vitro passage, but was significantly lower than that of age-matched normal cells (2.1 +/- 0.8, P less than 0.001). In progeria cells, the reduced stimulation of 2dG uptake upon addition of ILA was due to an increased basal rate of uptake (0.19 +/- 0.01 pmol [3H]2dG/min per mg protein vs. 0.13 +/- 0.01 in age-matched normal cells), and not to a decline in the maximal rate of uptake (0.26 +/- 0.01 vs. 0.27 +/- 0.02, respectively). Similar results were found for in vitro aging in cells from an old donor.
Serum prolactin and cortisol levels were measured in 24 patients entering the Royal Victoria Hospital infertility center both before and after a thorough physical examination that included a pelvic examination and a search for galactorrhea in both breasts. There was no significant change in the levels of prolactin or cortisol in the group as a whole in those with normal prolactin values and those with high basal prolactin values (P less than 0.05). The possible role of stress in the mediation of occasional elevation of basal prolactin values is discussed in relation to the serum cortisol levels.
Data regarding the incidence and effect of maternal thyroid antibodies on neonatal thyroid function are conflicting. In order to elucidate this aspect, antimicrosomal thyroid antibodies were measured: (1) in cord serum of a normal populations, (2) in the eluate of blood spots of infants with normal filter paper spot T4 and TSH, (3) in the eluate of blood spots from our recalled population (low T4 and normal TSH), and (4) in serum of detected hypothyroid infants. The incidence of MCA with titer greater than 1/40 in cord sera was 8% (115 of 1.383). There was no statistical difference in cord serum T4' T3' or TSH concentrations in these newborn infants compared to the MCA negative population. In 1,000 spots with normal T4 and TSH, 11 or 1.1% were positive for MCA. In 1,630 spots with low T4' 18 positive cases were discovered, or 1.1%. There was excellent correlation between maternal MCA titers and newborn infant titers either in sera or spots when paired samples were available. Finally, only one of 104 detected infants with primary hypothyroidism had detectable MCA. These results indicate a high incidence (8%) of MCA in our presumed normal newborn population, MCA does not decrease serum T4' T3' and TSH concentration or filter paper spot T4 and TSH, and thyroid autoimmunity is not a frequent cause of congenital hypothyroidism.
Oral administration of the serotonin precursor, L-tryptophan, to normal male volunteers (n = 7) in a dose (3 g) sufficient to increase free plasma tryptophan concentrations more than 12-fold had no significant effect on basal growth hormone secretion or on apomorphine HCL-induced (0.75 mg sc) peak growth hormone concentrations. These data suggest that, in man, tryptophan administration has little effect on central dopaminergic function, at least in the hypothalamic-pituitary axis and that serotonergic mechanisms have no major modulatory effect on dopamine-mediated growth hormone secretion.
We describe a simple method for evaluating thyroxine-binding globulin capacity and concentration from a single 1-cm blood spot on filter-paper used in a screening program for neonatal hypothyroidism. This method permits prompt diagnosis of about 90% of the infants with thyroxine-binding globulin deficiency in our abnormal low-thyroxine, low-thyrotropin population. There was excellent equivalence between results obtained by our method and by the method of Chopra et al. (J. Clin. Endocrinol. Metab. 35:565, 1972), and minimal overlap between the population with low thyroxine-binding globulin and the low-thyroxine, normal thyrotropin population. We recommend this method to all programs in which a primary thyroxine measurement is used in screening for congenital hypothyroidism.
Hypothyroid babies being breast-fed (12 cases) or bottle-fed (33 cases) have been compared. Anthropometric measurements at referral as well as biochemical values including plasma T4, T3, and thyroid-stimulating hormone were not significantly different. Bone maturation expressed as number of ossification centers or their surface were identical. Babies from both groups had similar psychologic performance at their first anniversay. It is concluded that breast-feeding does not protect against the deleterious effects of congenital hypothyroidism,.
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Five additional examples of partial deletion of the short arm of the X chromosome are reported. All of the patients had short stature. The presence of the other stigmata of Turner syndrome, including ovarian dysfunction, appeared to depend on the location of the deletion. Chromosomal analysis of girls with short stature (less than 140 cm), normal pubertal development, and regular menses may reveal that minor deletions of the short arm of the X chromosome are more frequent than has been previously reported.
Naloxone HCl (0.8 mg intravenously; n=9) or levallorphan tartrate (0.25 mg subcutaneously; n=5) had no effect on basal prolactin or growth hormone secretion in normal men. Neither narcotic antagonist inhibited the growth hormone secretory response to apomorphine HCl (0.75 mg subcutaneously). These findings suggest that narcotic antagonists do not block dopamine receptors in the hypothalamic-pituitary axis in man and that if these agents have antischizophrenic properties then these are not mediated by dopamine receptor blockade.
Clozapine had no effect on basal serum growth hormone concentrations in 10 schizophrenic patients but significantly inhibited the apomorphine-induced growth hormone increase that occurred in 7 subjects. Clozapine caused a slight (17%) but significant elevation in basal serum prolactin levels. These data suggest that in man clozapine, like other neuroleptics, blocks dopamine receptors, at least in the hypothalamic-pituitary axis.
The effect of benztropine on haloperidol-induced prolactin secretion was investigated in 10 normal male volunteers. Benztropine had no effect on basal prolactin secretion but significantly enhanced the increased induced by haloperidol. The magnitude of the enhancement, however, was relatively small. These data suggest that in man cholinergic mechanisms have no effect on basal prolactin secretion but exert a weak inhibitory effect under conditions of dopamine receptor blockade. Differences in intrinsic anticholinergic properties may account for some of the variations in potency of different neuroleptics in increasing circulating prolactin concentrations.
From our experience in the screening of 212,000 newborn infants, we have devised a flow chart for processing T4 and TSH measurements obtained from initial filter paper blood spots. To date, all infants with thyroid dysfunction or TBG deficiency have been detected. Of the population screened, 1.84% require a spot TSH determination, and 1.1% require repeat determinations of T4.
Serum prolactin (PRL) and human growth hormone (HGH) were assessed before, and three hours after oral administration of 2.5 mg of bromocriptine in 39 hospitalized geriatric patients with organic brain syndrome. Serum PRL concentrations decreased significantly irrespective of initial values (also in the 7 geriatric control subjects), but HGH levels were low in all patients and did not change during the three hours after administration of bromocriptine. Closer scrutiny of the HGH responses to bromocriptine in 5 patients and 5 controls showed that the serum HGH response was more variable among the patients than among the controls. The findings are discussed in relation to neuroendocrine changes associated with aging, institutional living, and mental disease.
The effect of lithium on apomorphine-induced growth hormone secretion and haloperidol-induced prolactin secretion was examined in eight male subjects without history of manic-depressive illness. Lithium had no effect on baseline or drug-induced changes in serum growth hormone or prolactin concentrations. These data suggest that lithium does not alter hypothalamic-pituitary dopamine receptor function.