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Biomedical subjects

L Lazarus

Publications and source records attributed to L Lazarus.

At least 37 records · Page 2Linked to original sources
PubMed1988

Visual field area in phakic, aphakic, and pseudophakic individuals.

Goldmann perimetry was done on 11 pseudophakic subjects and results were compared to those of age-matched phakic subjects and a third group of aphakic individuals who were wearing rigid gas permeable contact lenses. Testing showed that the I-3 and I-4 fields of the subjects who had had cataract surgery were generally constricted when compared to the normal phakic population. Possible explanations for this include media clarity not being as important a factor in determining field size as was previously thought, peripheral retinal changes, and implant material affecting contrast sensitivity.

Aged↗
PubMed1988

A comparison of the dynamics of secretion of human growth hormone and LH pulses.

Patterns of hypothalamic stimulation causing pituitary hormone release cannot be studied directly in humans; one possible approach is to make inferences from the nature of the response of the target organ as revealed by patterns of pituitary hormones in blood. Replicated, precise assay of LH in frequently sampled blood of women at differing stages of the menstrual cycle has demonstrated previously that secretion of this hormone is compatible with a model of discrete, instantaneous episodes of LH output, which are assumed to be stimulated by isolated bursts of increased stimulatory hypothalamic gonadotrophin-releasing hormone. However, similarly detailed measurements of the dynamic secretion patterns of GH in women reported here, revealed much slower rates of increase of GH concentrations (median time to maximum concentration 38 min) in comparison with LH (13 min) assayed in the same blood samples. These rise rates of GH were uncorrelated with the final amplitude of the peak and were observably discontinuous in half the peaks. Simultaneous i.v. injection of a bolus of mixed GRF and GnRH produced similar dynamics of pituitary release of GH and LH. Thus differences in patterns of natural release of the two hormones appear to be contributed to by differences in the modes of hypothalamic stimulation. Current understanding of control of GH release in animal models suggests that the slow-rising, frequently discontinuous natural peaks of GH in human blood are likely to be caused by interaction between the withdrawal of inhibitory hypothalamic somatostatin and the increased secretion of stimulatory GRF.

Female↗
PubMed1987

Methionine oxidation in human growth hormone and human chorionic somatomammotropin. Effects on receptor binding and biological activities.

The oxidation of the methionine residues of human growth hormone (hGH) and human chorionic somatomammotropin (hCS) to methionine sulfoxide by hydrogen peroxide has been studied. The kinetics of oxidation of individual methionine residues has been measured by reverse-phase high pressure liquid chromatography tryptic peptide mapping. Met-170 is completely resistant to oxidation in both hormones. The other 3 methionine residues in hCS (Met-64, Met-96, and Met-179) have markedly different reaction rates. Oxidation of the methionine residues does not appear to cause gross conformational changes in either hGH or hCS, as judged by CD and 1H NMR spectroscopy. Oxidation of Met-14 and Met-125 in hGH has little effect on affinity of the hormone for lactogenic receptors or on its potency in the Nb2 rat lymphoma in vitro bioassay for lactogenic hormones. The oxidation of Met-64 and/or Met-179 in hCS reduces profoundly both its affinity for lactogenic receptors and its in vitro biological potency. It is inferred by induction that residues 64 and/or 179 are critical for the binding of both hGH and hCS to lactogenic receptors and the expression of lactogenic biological activity.

Animals↗
PubMed1986

Normal lactotroph sensitivity to graded low-dose dopamine infusions in pathological hyperprolactinemia.

The question as to whether there is lactotroph resistance to dopamine (DA) in pathological hyperprolactinemia (PHP) is unresolved. Previous studies utilizing low-dose DA infusions to study lactotroph function have not considered the diurnal changes in prolactin (PRL) secretion that occur in normals but which are lost in PHP. As PRL levels show a fall in the hours after waking, studies performed during this time of day will falsely show a greater fall of PRL in normals than in PHP patients. The aim was to readdress the issue of lactotroph sensitivity using a study designed to minimize the problem arising from diurnal PRL changes. Eight normal subjects, 17 patients with PHP, and 6 hyperprolactinemic patients with nonfunctioning pituitary tumors (NFTs) were studied with three graded doses of DA - (0.01, 0.05, and 0.5 micrograms/kg X min) - by relating the changes induced by each dose to the maximal spontaneous fall in PRL that occurred during a 3-hour control saline study. The mean +/- SE maximal fall in PRL during control saline infusion to 46.0 +/- 4.1% of basal in normal subjects was significantly greater (p less than 0.001) than the fall in patients with PHP (88.0 +/- 1.0%) or NFTs (87.5 +/- 2.6%). The apparent fall in PRL was significantly greater in normals during the two lower infusion doses, but not at the highest dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Modulation of lactogenic receptors by progestins in cultured human breast cancer cells.

Progesterone receptors (PgR) are present in many breast cancers, but few specific actions of progestins in breast cancer cells have been reported. We now report that progestins specifically modulate lactogenic receptor expression in cultured T-47D and MCF-7 human mammary carcinoma cells. When T-47D cells were preincubated for 24 h with 1 nM medroxyprogesterone acetate (17 alpha-acetoxy-6 alpha-methyl-4-pregnene-3,20-dione), specific binding of [125I]human GH ([125I]hGH) and [125I]human PRL was increased to 205 +/- 22% (+/- SE) (P less than 0.01) and 175 +/- 32% (P less than 0.05), respectively, of that in control cultures. There was no significant effect on cell number and no significant enhancement of specific binding of [125I]porcine insulin, [125I]salmon calcitonin, [125I]human transferrin, or [3H] Concanavalin A. Lactogenic receptor number was increased from 6,490 +/- 500 (n = 12) to 13,180 +/- 3,270 (n = 7; P less than 0.01) sites/cell, with no significant change in affinity for hGH. Progesterone, which is readily metabolized by these cells, was less potent than the synthetic progestins (medroxyprogesterone acetate, R 5020 (17 alpha, 21-dimethyl-19-norpregn-4,9-diene-3,20-dione), and ORG 2058 (16 alpha-ethyl-21-hydroxy-19-norpregn-4-en-3,20-dione), but physiological concentrations of progesterone (1 nM) significantly enhanced specific binding of [125I]hGH to 153 +/- 23% of the control value (n = 6; P less than 0.05). Physiological concentrations of androgens, estrogens, and glucocorticoids had no significant effect. MCF-7 cells were considerably less sensitive to these effects of progestins than T-47D cells, probably due to the lower PgR concentration in MCF-7 cells. These observations, which indicate that lactogenic receptor expression is controlled, at least in part, by progestins in these mammary carcinoma cell lines, may have important implications in the management of human breast cancer, where high levels of this receptor may reflect a functional PgR and a highly hormone-dependent phenotype.

Breast Neoplasms↗
PubMed1986

Progestin regulation of epidermal growth factor receptor in human mammary carcinoma cells.

Epidermal growth factor (EGF) receptors are present in human breast cancer and probably mediate the effects of EGF and the autocrine effects of alpha-transforming growth factors, produced by breast cancer cells. Steroid hormones influence the growth of some human cancers, and both direct and indirect effects on cell proliferation have been proposed. One potential indirect effect of steroids would be to augment sensitivity to other endocrine and autocrine factors by up-regulation of their receptors. We therefore investigated the effects of various steroids on EGF receptor expression in T-47D, MCF-7, and BT 20 human mammary carcinoma cells in culture. Preincubation of T-47D cells for 24 h with a series of androgens, estrogens, glucocorticoids, and progestins resulted in a significant enhancement of specific 125I-EGF binding in the presence of progestins only. Increased binding of EGF was associated with neither a change in cell number nor changes in the specific binding of concanavalin A, insulin, or calcitonin but was accompanied by an increase in lactogenic receptor expression. When assayed at 20 degrees C, increased EGF binding was due to an increase in receptor number (33,380 +/- 7,410 sites/cell in control cultures; 67,460 +/- 20,330 sites/cell in cultures treated with 1 nM medroxyprogesterone acetate for 24 h; P less than 0.05) without a change in receptor affinity. Two- to 3-fold increases in receptor number were also apparent when binding was measured at 4 degrees C, indicating that the effect was due to an increase in expression of receptor at the cell surface rather than progestin effects on internalization and degradation. These data illustrate that the expression of EGF receptor in some breast cancer cells is regulated in part by mechanisms mediated via the progesterone receptor, since the effect was confined to progestins, potency among a series of progestins was correlated with their affinities for progesterone receptor, and sensitivity among the three cell lines studied was related to the presence and concentration of cellular progesterone receptor.

Androgens↗
PubMed1986

Error in laboratory reference limits as shown in a collaborative quality-assurance program.

Laboratories participate in collaborative quality-assurance programs to maintain and improve the quality of their diagnostic assays, but little attention has been paid to diagnostic quality in these programs. We used a national quality-assurance program to assess the quality of laboratory reference intervals as exemplified by triiodothyronine, thyroxin, and thyrotropin immunoassays. The limits of the reference intervals used by laboratories bear virtually no relationship to laboratory bias, i.e., whether assays read "high" or "low." Further, correcting assay results from different laboratories for the reference limits used increases rather than decreases interlaboratory scatter. We conclude that the analytical quality of immunoassays now exceeds the quality of the reference limits supplied to clinicians to assist diagnosis, and that nationally or internationally defined reference limits would therefore provide more information at less cost than do individual laboratory reference limits.

Humans↗
PubMed1985

Regulation of growth hormone and epidermal growth factor receptors by progestins in breast cancer cells.

A 24 hr incubation of T-47D human breast cancer cells with R5020, a synthetic progestin, resulted in a 200-250% increase in the specific binding of human growth hormone (hGH) and epidermal growth factor (EGF) by these cells. This effect was specific for progestins in that similar responses were observed with progesterone, medroxyprogesterone acetate and ORG 2058 but no significant increases in hGH or EGF binding were observed in cells incubated with testosterone, estradiol or hydrocortisone. Increased binding was due to an increase in the concentration of receptors (hGH, control = 6,490 +/- 500, progestin treated = 13,180 +/- 3,270 sites/cell; EGF, control = 33,380 +/- 7,410, progestin treated = 67,460 +/- 20,330 sites/cell) while the affinity constants for the hormone-receptor interactions were unchanged by progestin treatment. The specific binding of insulin, calcitonin, transferrin and concanavalin A was unaffected by these treatments. It is concluded that expression of hGH and EGF receptors in this breast cancer cell line is regulated by progestins.

Breast Neoplasms↗
PubMed1985

The interaction of trh and dopaminergic mechanisms in the regulation of stimulated prolactin release in man.

The manner by which dopaminergic and TRH mechanisms interact to control PRL release is not known. Whilst dopamine receptor antagonists and TRH both release PRL, it is not known if the PRL released by these two mechanisms reflects similar aspects of physiological control, or if PRL responses to these mechanisms of release can be dissociated. We addressed this question by studying the PRL responses to maximal stimulatory dose of TRH and domperidone (a DA receptor antagonist), which were administered sequentially, simultaneously or separately on different occasions. Six normal volunteers undertook three sets of studies: (1) standard PRL stimulation tests to 400 micrograms TRH, 5 mg domperidone or simultaneous TRH/domperidone administration, (2) domperidone bolus-infusion study in which either 5 mg domperidone or 400 micrograms TRH was administered i.v. at 120 min during a 240 min infusion of domperidone (50 micrograms/min) which was preceded by a 5 mg i.v. bolus of the drug, and (3) TRH bolus-infusion study in which domperidone or TRH was administered i.v. at 120 min during a 240 min infusion of TRH (0.4 micrograms/min) which was preceded by a 400 micrograms i.v. bolus of the drug. In Study 1, simultaneous TRH/domperidone administration induced an incremental rise in PRL (5195 +/- 940 mIU/l) which was significantly greater (P less than 0.0005) than with either domperidone (3730 +/- 825 mIU/l) or TRH (1335 +/- 300 mIU/l) alone. In study 2, TRH administration at 120 min resulted in a significant rise (P less than 0.01) in PRL (delta PRL 960 +/- 232 mIU/l) whilst the second dose of domperidone did not, thus suggesting that the initial bolus and subsequent infusion had resulted in complete DA receptor blockade. In Study 3, domperidone administered at 120 min induced a marked rise in PRL (delta PRL 3609 +/- 963 mIU/l). In contrast, the corresponding TRH stimulus resulted in a small rise (delta PRL 142 +/- 32 mIU/l) suggesting that the PRL release induced by the initial bolus and subsequent infusion had been near maximal. Thus, TRH is able to induce significant PRL release in the presence of maximal DA receptor blockade, and domperidone, in the presence of maximal TRH stimulation, is also capable of inducing significant PRL release. These observations together with the ability of TRH/domperidone to induce a greater PRL response than either agent alone, suggest that each stimulus has a specific releasing action on a fraction of intracellular PRL which is not accessible to the other.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1985

Long-term bromocriptine therapy may restore the inhibitory control of prolactin release in some patients with pathological hyperprolactinemia.

While bromocriptine is effective in controlling hyperprolactinemia, it is not known if bromocriptine therapy can restore the abnormal regulation of prolactin (PRL) release found in patients with pathological hyperprolactinemia. We report 15 hyperprolactinemic patients treated for a mean duration of 5.5 +/- 0.6 years (mean +/- SE) in whom stimulation tests to assess PRL control mechanisms [thyrotropin releasing hormone (TRH) and metoclopramide] were performed before and at least one month after withdrawal of bromocriptine therapy. The basal PRL level after withdrawal of bromocriptine therapy was significantly lower (p less than 0.001) than that before therapy. All patients had blunted PRL stimulatory responses to TRH and metoclopramide (% delta 16.0 +/- 5.6%) before treatment. After withdrawal of bromocriptine, PRL responses to stimulatory tests were significantly improved in seven patients (termed 'responders', % delta 376 +/- 55%) but remained unchanged in eight patients (termed 'non-responders', % delta 9.2 +/- 3.0%). Basal PRL levels were significantly lower (p less than 0.01) in responders (290 +/- 35 mIU/l) than in non-responders (10360 +/- 6790 mIU/l). Four of the responders have maintained normoprolactinemia and normal stimulated PRL responses for 15 months to three years following cessation of bromocriptine therapy and appear to be in remission. Favourable factors amongst the responders were the female sex, absence of a macroadenoma, and a pre-treatment PRL level below 3000 mlU/l. PRL stimulation tests performed before therapy could not predict which patients would respond. No relationship was found between duration of therapy, or age at presentation, and improvement after bromocriptine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMed1985

Studies on the central and peripheral dopaminergic control of PRL secretion in man: failure to demonstrate the existence of a dopamine-mediated prolactin-inhibiting factor.

The existence of a putative central prolactin-inhibiting factor (PIF) distinct from dopamine (DA) but dependent on DA mechanisms for release has been suggested from recent animal studies. We investigated the possibility of the existence of such a PIF in man by combining the use of monoiodotyrosine (MIT), an inhibitor of central DA synthesis, domperidone, a DA receptor antagonist that does not enter the blood-brain barrier and DA itself. 6 normal volunteers underwent three sets of studies: (1) PRL stimulation test to 400 micrograms TRH i.v., 1 g MIT orally or 5 mg domperidone i.v., (2) peripheral DA receptor blockade study in which either domperidone, MIT or TRH was administered at 120 min during a 240-min domperidone infusion (50 micrograms/min) which was preceded by a 5-mg bolus dose of domperidone i.v. and, (3) DA infusion study in which MIT was administered at 120 min during a 240-min infusion of DA in a dose (0.5 microgram/kg X min) known to elevate peripheral DA concentration to levels reported for pituitary portal plasma. In the PRL stimulation tests, the mean +/- SE peak response was significantly greater (p less than 0.002) with domperidone (3,900 +/- 840 mIU/l) than with MIT (1,880 +/- 400 mIU/l) or TRH (2,094 +/- 450 mIU/l). In the peripheral DA receptor blockade study the initial domperidone-induced PRL response was not sustained during the domperidone infusion. Neither a second dose of domperidone nor MIT administration at 120 min resulted in a significant release of PRL.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Enhanced hypothalamic dopaminergic inhibition of LH, TSH and GH release in patients with pathological hyperprolactinaemia.

Recent studies have suggested that patients with prolactinomas have a defect in the central regulation of prolactin (Prl) release but it is not clear whether the defect results from a true loss of hypothalamic dopamine activity or from a functional inability of inherent dopaminergic inhibition to be mediated effectively. We have studied this question by the use of monoiodtyrosine (MIT, 1 g orally), a specific inhibitor of central dopamine synthesis to remove dopaminergic inhibitory control of Prl release in 10 normal ovulating women, 8 women on oral contraceptive steroids (OC) and 8 patients with pathological hyperprolactinaemia (PHP). LH, TSH and GH were also measured during the study in view of recent reports suggesting that dopaminergic mechanisms may be involved in modulating their secretion. Subjects on OC had a significantly higher (P less than 0.05) mean basal Prl (353 +/- 34 vs 280 +/- 26 mIU/l) and a significantly greater (P less than 0.05) peak response (incremental change 2270 +/- 300 mIU/l to MIT than normal controls (1320 +/- 220 mIU/l). Patients with PHP had a highly significantly blunted (P less than 0.001). Prl response (incremental chane 290 +/- 95 mIU/l) compared to controls. MIT administration caused a significant increase in LH (P less than 0.05), TSH (P less than 0.01) and GH (P less than 0.01) in patients with PHP but not in normal or OC-treated subjects. The augmented Prl response of subjects on OC is consistent with an increase in dopaminergic inhibitory control of Prl release. The lack of Prl response in subjects with PHP is indicative of a functional loss of dopaminergic control.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1984

Effects of hypophysectomy and subsequent growth hormone replacement in the rat on the ability of serum to stimulate proliferation of human and mouse (BALB/c 3T3) fibroblasts.

The ability of cultured human fibroblasts to synthesize and secrete a mitogenic, somatomedin C-like peptide suggests that human fibroblasts unlike certain other cell lines may not require exogenous somatomedin for cell proliferation. The aim of this study was to examine the effects of hypophysectomy and subsequent growth hormone (GH) replacement on the ability of rat serum to stimulate proliferation and DNA synthesis in cultured human fetal skin fibroblasts. For comparison we have also examined the effects of serum from hypophysectomized (hypox) and GH-replaced hypox rats on mouse BALB/c 3T3 fibroblasts, a cell line which has been shown to require exogenous somatomedin (SM) for DNA synthesis and cell proliferation. Human fibroblast proliferation and DNA synthesis (measured as thymidine incorporation) were significantly enhanced (P less than 0.025) when these cells were cultured in low concentrations of hypox rat serum compared to normal rat serum. When thymidine incorporation into DNA was expressed in terms of a normal rat serum pool (arbitrarily assigned a potency of 1 unit/ml), serum from hypox rats was significantly more potent than serum from normal rats (1.52 +/- 0.16 (SEM) vs. 0.99 +/- 0.10 units/ml, P less than 0.0125). Replacement treatment of hypox rats with human GH, 0.2 IU/100 g body weight/day or 0.4 IU/100 g body weight/day decreased the potency of the rat serum in terms of stimulation of thymidine incorporation from 1.52 +/- 0.16 to 1.30 +/- 0.14 and 1.08 +/- 0.06 units/ml respectively. In contrast serum from untreated hypox rats was significantly less potent than normal rat serum in stimulating BALB/c 3T3 DNA synthesis (0.36 +/- 0.06 vs. 1.04 +/- 0.16 units/ml, P less than 0.0025).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Dopaminergic control of gonadotrophin secretion in normal women and in patients with pathological hyperprolactinaemia.

The role of dopaminergic mechanisms in the control of gonadotrophin secretion in normal and hyperprolactinaemic subjects is controversial. Whilst bromocriptine, a potent dopamine agonist, has been used to restore normal gonadotrophin secretion in subjects with pathological hyperprolactinaemia (PHP), dopamine and dopamine agonists have been reported to suppress basal and stimulated gonadotrophin release. We therefore investigated the importance of dopaminergic control of gonadotrophin secretion by studying LH, FSH and PRL responses in normal and PHP subjects to central dopamine synthesis inhibition using monoiodotyrosine (MIT) and to a 4 h dopamine infusion designed to elevate peripheral plasma dopamine concentration to levels reported for pituitary portal plasma (1-6 ng/ml). MIT administration resulted in a significant release of PRL (peak increment 520 +/- 84% above basal) but not of LH or FSH in normal subjects. In PHP subjects there was a blunted PRL response (peak 13.3 +/- 3.5%) to MIT administration and significant LH (P less than 0.05) but not FSH release. Dopamine infusion (0.5 microgram/kg/min) resulted in suppression of PRL (min 19 +/- 3% of basal) but not of LH or FSH. A rebound of PRL (peak 188 +/- 68% of basal) but not LH or FSH occurred on cessation of dopamine. There was an apparent rise in LH (P less than 0.02 vs. normals) but not FSH in PHP patients during dopamine infusion. Plateau dopamine levels achieved during the infusion were 2.9 +/- 0.3 ng/ml and 5.9 +/- 0.8 ng/ml in normal and PHP subjects respectively. The responses to MIT show that dopamine functions as an inhibitor of PRL but not of LH or FSH in normal subjects. In PHP patients the responses suggest increased dopaminergic inhibition of LH release but loss of inhibitory control of PRL release. Physiological concentrations of plasma dopamine do not significantly inhibit LH or FSH release in normal subjects but paradoxically results in an apparent release of LH in PHP patients. We conclude that dopamine mechanisms do not play a significant role in modulating gonadotrophin release in normal subjects. In PHP patients, PRL feedback results in increased hypothalamic dopamine activity which in turn inhibits LH release. We conclude that the inhibitory action of dopamine on PRL release restores LH secretion by removing central dopaminergic inhibition through hypothalamic feedback of PRL.

Adult↗
PubMed1984

Reversible uremia due to bilateral ureteral obstruction from tuberculosis. Case report and review.

An El Salvadoran man with reversible uremia secondary to genitourinary tuberculosis is described. The literature of genitourinary tuberculosis is also reviewed with emphasis on the pathology and infrequency of renal failure in this setting. Although the total number of cases of tuberculosis and pulmonary disease in particular is declining, the prevalence of extrapulmonary TB is not. In addition, the incidence of TB in recent immigrants to the United States is extremely high. Thus, the finding of tuberculosis should prompt investigation to rule out genitourinary disease which can be clinically silent in a large percentage of the cases.

Antitubercular Agents↗
PubMed1984

The mouse fibroblast growth hormone receptor: ligand processing and receptor modulation and turnover.

The recent observation that adipose conversion of mouse 3T3 fibroblasts is stimulated by physiological concentrations of human GH (hGH) and rat GH in vitro suggested that this cell line may be suitable for the study of GH-receptor interactions. The aim of this study was to examine the binding and subsequent processing of [125I]iodo-hGH by BALB/c 3T3 mouse fibroblasts. Binding of [125I]iodo-hGH to 3T3 fibroblasts was time and temperature dependent. Apparent steady state binding was achieved after 1 and 2 h at 37 and 30 C, respectively. At 37, 30, and 20 C specifically bound [125I]iodo-hGH became increasingly resistant to removal by acid treatment (0.15 M NaCl/0.05 M glycine, pH 2.5). In contrast at 4 C or at higher temperatures in the presence of metabolic inhibitors, a greater proportion of specifically bound hGH was removed by acid treatment. Inclusion of 0.2 mM chloroquine in the incubation medium resulted in significantly more accumulation of trichloroacetic acid (TCA)-precipitable radioactivity compared to control cells without affecting the shift of radioactivity from the acid-elutable to the acid-inaccessible compartment. After removal of [125I]iodo-hGH from the medium there was a rapid loss of radioactivity (t 1/2 = 36.5 +/- 7.2 min, SE, n = 3) from the cell monolayer with a concomitant appearance in the medium of TCA-soluble radioactive species. Chloroquine reduced the rate of efflux of radioactivity from the monolayer (t 1/2 = 4.5 +/- 0.6 h, n = 3) and the appearance of TCA-soluble material in the medium. The half-time of GH receptor loss after inhibition of protein synthesis with cycloheximide (0.1 mM) was 1.25 +/- 0.14 h, n = 3). In contrast half-time of net receptor synthesis calculated from the recovery of specific [125I]iodo-hGH binding capacity after ligand-induced down-regulation was 10.2 +/- 1.5 h, n = 3). These data reveal that after binding of [125I]iodo-hGH to specific cell surface receptors there is rapid irreversible binding of GH to its receptor with a resultant reduction in receptor concentration. Degradation of [125I]iodo-hGH occurs intracellularly and involves processes which are inhibited by lysosomotropic agents. On the basis of these studies we conclude that the binding and subsequent processing of GH by 3T3 fibroblasts is qualitatively similar to that described for other polypeptide hormones and growth factors in this and other cell lines.

Animals↗
PubMed1984

Dopamine infusion studies in patients with pathological hyperprolactinemia: evidence of normal prolactin suppressibility but abnormal dopamine metabolism.

The cause of pathological hyperprolactinemia (PHP) is not known, although it has been postulated that lactotroph refractoriness to dopamine (DA) is an important factor. We, therefore, studied PRL suppressibility in response to iv DA administered in a dose designed to achieve peripheral plasma DA concentrations in the range reported in rat pituitary portal plasma. Nine normal subjects and 14 patients (8 with probable microadenomas and 6 with macroadenomas) with PHP were studied during a 4-h infusion of 0.5 micrograms/kg X min DA. Serum PRL levels decreased in normal subjects to 18 +/- 3% (mean +/- SEM) of initial basal levels, not significantly different from the fall to 22 +/- 2% of basal levels found in patients with PHP. Maximal PRL suppression in patients with probable microadenomas (21 +/- 2%) was not significantly different from that in those with macroadenomas (22.8 +/- 2.0%). Upon cessation of DA infusion, there was a rapid rebound in PRL release, which was significantly greater (P less than 0.05) in patients (155 +/- 15%) than in normal subjects (118 +/- 13%). Plasma DA levels were measured by gas chromatography/mass spectroscopy and were significantly higher (P less than 0.05) in patients than in normal subjects during the infusion. The MCR for DA in normal subjects (12.5 +/- 2.8 liters/kg X h) was significantly greater (P less than 0.005) than that in patients (6.2 +/- 0.5 liters/kg X h). The data show that the release of PRL in patients with PHP is not refractory to physiological concentrations of DA, but that there is an abnormality of peripheral DA metabolism in these patients. We conclude that the development of PHP is unlikely to be due to insensitivity of lactotrophs to endogenous DA and that patients with PHP have a systemic disturbance of DA metabolism.

Adenoma↗