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Biomedical subjects

F Maloof

Publications and source records attributed to F Maloof.

At least 37 records · Page 2Linked to original sources
PubMed1981

Production and release of thyrotropin and its subunits by monolayer cultures containing bovine anterior pituitary cells.

We have developed a dispersed cell monolayer system derived from bovine anterior pituitary glands. Fresh 1- to 6-week-old calf anterior pituitaries were mechanically and enzymatically dispersed and incubated with Dulbecco's Modified Minimal Essential Medium containing 10% hypothyroid goat serum. The media and cell extracts from confluent monolayers were analyzed for bovine TSH and free alpha, and TSH beta subunits by specific homologous RIAs. Basal levels of TSH, free alpha, and free TSH beta subunits in the media were 6.2 +/- 0.3, and 0.95 +/- 0.05 ng/10(6) cells . 24 h, respectively. Hence, an 8- to 10-fold excess of free alpha over free TSH beta subunits was released into the medium. Intracellular basal levels of TSH, free alpha, and free TSH beta subunits were 27.6 +/- 1.7, 10.7 +/- 0.2, and 2.6 +/- 0.3 ng/10(6) cells . 24 h, respectively, and indicated a 3- to 4-fold excess of free alpha over free TSH beta subunits within the cells. The total alpha-subunit to total beta-subunit ratio was 2:1. TRH stimulated release of TSH and its subunits in a dose-dependent fashion, with a half-maximal dose of 2 nM and a maximal response dose of 10 nM. Stimulation with 100 nM TRH increased the levels of TSH, free alpha, and free TSH beta subunits (450-900%, 180-200%, and 300-400%, respectively) in medium, with concomitant decreases within cells. Treatment with thyroid hormones decreased basal and blunted TRH-stimulated levels of TSH and its subunits in medium but had no effect on intracellular stores. However, large doses of T4 (25 nM) or T3 (1 nM) did not completely abolish the TRH (100 nM)-stimulated hormone response. TRH and thyroid hormones affect the release of TSH and TSH beta to a greater extent than they do the alpha-subunit. Finally, total alpha and TSH beta subunit production was increased with TRH stimulation and decreased with thyroid hormone exposure. Thus, an in vitro system to study the net production and secretion of TSH and its subunits in the normal pituitary thyrotrope has been established. (Endocrinology 108: 387, 1981)

Animals↗
PubMed1981

Congenital goiter and the development of metastatic follicular carcinoma with evidence for a leak of nonhormonal iodide: clinical, pathological, kinetic, and biochemical studies and a review of the literature.

We report a large kindred of patients with congenital goiter, followed for 15 yr, in which two siblings (one male and one female) developed metastatic follicular thyroid carcinoma. These two patients were evaluated by iodine kinetic analysis. None of the classical defects of T4 biosynthesis was present in either patient. Rather, both patients had extremely rapid rates of iodine turnover, with elevated 131I uptake and excessive spillage of iodide in the urine. Serum iodoalbumin was present, probably as a nonspecific result of glandular hyperplasia. Iodine kinetic analysis after the ingestion of potassium perchlorate and methimazole was compatible with a leak of nonhormonal iodide from the thyroid. It is not possible to determine whether this iodide leak is the primary pathogenetic defect or is secondary to another unidentified abnormality. The unprecedented development of metastatic thyroid cancer in patients with congenital goiter occurred, in both instances years after subtotal thyroidectomy without thyroid hormone replacement therapy, suggesting a role for TSH in the genesis of human thyroid cancer. On the basis of our study of these patients and a review of the literature, we conclude that TSH is likely to be a factor in the induction of human follicular thyroid carcinoma.

Adenocarcinoma↗
PubMed1981

Peripheral responses to thyroid hormone before and after L-thyroxine therapy in patients with subclinical hypothyroidism.

Twenty patients with serum levels of T4 and T3 within the normal range but with elevated serum concentrations of TSH were evaluated before and after treatment with L-T4. This therapy increased serum T4 (5.5 +/- 1.1 to 8.8 +/- 1.8 microgram/dl) and T3 (116 +/- 20 to 137 +/- 28 ng/dl) levels. Cardiac systolic time intervals (STI) were significantly (P less than 0.01) reduced by this therapy. The preejection period (123 +/- 18 to 114 +/- 14 msec; n = 12), the change in preejection period (+17 +/- 17 to +6 +/- 15 msec; n = 12), the ratio of preejection period to left ventricular ejection time (0.412 +/- 0.068 to 0.357 +/- 0.063 msec; n = 12), and the interval from the Q wave of the electrocardiogram to the pulse wave arrival time at the brachial artery (224 +/- 10 to 200 +/- 13 msec; n = 10) were consistently reduced. Cardiac STI were significantly correlated with serum TSH and T4 levels, but not with serum T3 levels. Normalization of serum TSH levels was associated with changes in QKd measurements even in those patients with minimal elevations in serum TSH. These studies demonstrate that patients having the combination of elevated TSH but T4 and T3 levels in the normal range have alterations in STI which can be changed significantly by L-T4 in doses which normalize TSH secretion. These data suggest that such patients have a mild form of primary hypothyroidism.

Adult↗
PubMed1981

The effect of amoxapine and imipramine on serum prolactin levels.

The effect of traditional tricyclic antidepressants on serum prolactin levels is controversial. In a five-week double-blind study of depressed outpatients, imipramine hydrochloride therapy did not lead to any significant change in serum prolactin levels. In contrast, amoxapine, a new antidepressant, produced significant elevations in serum prolactin levels in female and in male patients. Amoxapine may block dopamine receptors in central tuberoinfundibular pathways, which would account for its prolactin-elevating activity. On the other hand, imipramine and other traditional tricyclic antidepressants do not affect dopamine transmission, do not raise serum prolactin levels, and are not effective antipsychotic drugs.

Adult↗
PubMed1980

Therapy of primary hypothyroidism with L-triiodothyronine: discordant cardiac and pituitary responses.

Cardiac systolic time intervals were studied in ten patients with primary hypothyroidism before and during therapy with increasing doses of oral L-triiodothyronine (L-T3). Therapy was increased sequentially from 10, 20, 25 to 50 microgram of L-T3 daily on a monthly basis. On L-T3, 20 to 25 microgram/day, cardiac systolic time intervals and other peripheral responses to thyroid hormone including serum cholesterol concentration, serum creatine phosphokinase (CPK) activity, and basal metabolic rate had normalized. However, serum thyrotrophin (TSH) levels and peak TSH responses to thyrotrophin-releasing hormone (TRH) remained elevated on these doses of L-T3. As the dose of L-T3 was increased from 20 to 50 microgram/day, mean basal serum TSH levels decreased from 55 to 16 microunits/ml, and the peak TSH response to TRH decreased from 243 to 58 microunits/ml (P less than 0.001) while systolic time intervals did not decrease further. Changing to L-thyroxine (L-T4) therapy at this point resulted in further suppression of TSH secretion, without significantly altering systolic time intervals or the other peripheral responses to thyroid hormone. These data suggest (a) that some biological responses to thyroid hormone were normalized on lower doses of L-T3 than were required to normalize TSH secretion, and (b) that higher doses of L-T3 or substituting L-T4 therapy could suppress TSH secretion further without altering the other peripheral responses to thyroid hormone.

Adult↗
PubMed1979

The relationship between endogenous hyperprolactinaemia and plasma aldosterone.

It has been suggested that prolactin is a regulator of aldosterone secretion. In order to test this hypothesis, we measured prolactin, thyrotrophin and aldosterone by radioimmunoassay and plasma renin activity by the radioimmunoassay of angiotensin I in eight normal women before and after the intravenous injection of 200 microgram of thyrotrophin releasing hormone (TRH). Prolactin increased from 4.1 +/- 1.1 ng/ml (mean +/- SE) to a peak of 27.4 +/- 3.8 (P less than 0.005) at 15 min following TRH. Plasma renin activity was not different from control levels (1.0 +/- 0.2 ng/ml/h) during the first hour following the administration of TRH, nor did the plasma aldosterone concentration differ significantly from the control levels (39 +/- 7 pg/ml) during this period. However, with upright posture, an increase in aldosterone (from 31 +/- 3 pg/ml at 1 h to 68 +/- 9 at 2 h, P less than 0.005) and in plasma renin activity (from 0.9 +/- 0.2 ng/ml/h at 1 h to 2.0 +/- 0.5 at 2 h, P less than 0.05) was noted, demonstrating a normal capacity to secrete aldosterone in these subjects. Similarly, no change in aldosterone was seen in nine patients with primary hypothyroidism given TRH, despite the fact that the increase in prolactin was greater than normal. Chronic hyperprolactinaemia was not associated with hyperaldosteronism in six patients with pituitary tumour. These data demonstrate that acutely or chronically elevated serum prolactin levels do not result in increased plasma aldosterone levels in humans.

Adrenal Cortex↗
PubMed1979

Augmentation of pituitary thyrotrophin response to thyrotrophin releasing hormone during subphysiological tri-iodothyroinine therapy in hypothyroidism.

Five hypothyroid patients are reported with increased pituitary TSH response to TRH during administration of T3. In one patient treated with intravenous T3, 50 micrograms daily for 10 days, the peak serum TSH and total pituitary TSH reserve after TRH increased coincident with increases in serum T3 and T4 levels and a decrease in the basal TSH concentration. In four patients treated with oral T3, the peak serum TSH and total pituitary TSH reserve after TRH increased during administration of subphysiological doses of T3. Peak serum T3 levels occurred 4 h after ingestion and increased progressively with increasing T3 doses. Serum TSH levels decreased modestly with the nadir at 4 h after T3 ingestion and then returned to basal levels at 24 h. Augmentation of TSH responses to TRH occurred simultaneously with decreases in serum cholesterol, as well as increases in the pituitary prolactin response to TRH, and increase in the GH and cortisol response to insulin induced hypoglycaemia where these responses could be studied. These data demonstrated a positive effect of subphysiological T3 therapy in these hypothyroid patients on the TSH response to TRH as well as increases in the responses of other pituitary hormones to stimulation.

Adult↗
PubMed1979

Metabolic clearance and production rates of prolactin in man.

Metabolic clearance rates (MCR) and production rates (PR) of prolactin (PRL) have been determined by the constant infusion to equilibrium technique in 11 normal subjects, 6 patients with hyperthyroidism, 4 patients with hypothyroidism, and 9 patients with hyperprolactinemia. PRL MCR was also determined tin four patients during dopamine infusion. Mean PRL MCR was 46 +/- 1 ml/min per m2 in women and 44 +/- 3 ml/min per m2 in men, and was significantly correlated with body mass (r = 0.84, P less than 0.001). In contrast with controls, PRL MCR was higher in hyperthyroidism (MCR = 52 +/- 8 ml/min per m2, P less than 0.05), was slightly lower in hypothyroidism (MCR = 38 +/- 10 ml/min per m2, P = NS), and was significantly correlated with serum thyroxine (r = 0.46, P less than 0.02). PRL MCR was lower than controls in hyperprolactinemia (MCR = 40 +/- 5 ml/min per m2, P less than 0.01) and was inversely correlated with serum PRL (r = -0.72, P less than 0.001). PRL MCR was not significantly changed by dopamine infusion. Mean PRL PR for women and men was 211 +/- 74 and 187 +/- 44 micrograms/d per m2, respectively (P = NS). In hyperthyroidism the PRL PR was elevated (PR = 335 +/- 68 micrograms/d per m2, P less than 0.02), but in hypothyroidism the increase (PR = 233 +/- 159 micrograms/d per m2) was not significant. In hyperprolactinemia the PRL PR was extremely high (PR = 31,000 +/- 29,000 micrograms/d per m2). Dopamine infusion decreased RPL PR from 270 to 66 micrograms/d per m2 indicating that its effect was on pituitary PRL secretion and not PRL metabolism. To evaluate possible circulating PRL heterogeneity that might arise during infusion, gel filtration of infusate and serum obtained during the MCR procedure was performed. Labeled monomeric PRL (peak III, Kav (partition coefficient) = 0.4) was partially converted to two larger forms (peaks I and II) in vivo. Peak I (Kav = 0) was 30--40% immunoprecipitable, although peak II (Kav = 0.2) was not immunoprecipitable. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of peak I resulted in greater than or equal to 90% conversion to peak III and restoration of full immunoactivity. Thus, peak I is a noncovalently linked aggregate that is partially immunoactive, and therefore able to alter MCR determinations. These studies demonstrate the impact of hormone heterogeneity on MCR estimations and suggest that gel filtration of immunoprecipitable material be an integral part of future MCR measurements.

Adenoma↗
PubMed1979

Thiourea and cyanamide as inhibitors of thyroid peroxidase: the role of iodide.

Thiourea, methylmercaptoimidazole, propylthiouracil, and thiouracil are all potent inhibitors of thyroid peroxidase (TPO)-catalyzed iodination. Unlike the cyclic thioureylenes, thiourea at 5 mM has no effect on guaiacol oxidation. If iodide is added to guaiacol assays containing thiourea, enzyme activity is lost. The latter observation may be explained as follows. In the presence of iodide, the iodinating species [TPO.Ioxid], oxidizes thiourea to formamidine disulfide. This product decomposes to cyanamide at neutral pH. We have shown cyanamide to be an inhibitor of the peroxidative and iodinating functions of TPO. Studies in rats demonstrate that doses of thiourea which completely inhibit in vivo protein-bound iodine formation have no irreversible effect on TPO, as measured by guaiacol peroxidation after removal of the thyroids. The major in vivo action of cyanamide is similar to that of thiourea. The data suggest that the primary in vivo and in vitro mode of action of thiourea is the reversible Ioxid-trapping mechanism. The anomalous inhibition of guaiacol peroxidation seen in the presence of thiourea plus iodide derives from the formation of formamide disulfide, followed by its nonenzymic decomposition to cyanamide.

Animals↗
PubMed1979

Alkaline phosphatase isoenzyme patterns in hyperthyroidism.

Fifteen of 36 hyperthyroid patients had elevation in serum alkaline phosphatase activity. There was no difference in mean thyroxine (T4), triiodothyronine (T3), age, or duration of illness between the groups with high alkaline phosphatase and normal alkaline phosphatase levels. After treatment, serum alkaline phosphatase levels rose as T4 levels declined; at 3 months, the mean serum alkaline phosphatase value rose from 7.1 Bodansky units to 10.3 Bodansky units (P less than 0.005), while the mean T4 value fell from 18 microgram/dl to 7.2 microgram/dl (P less than 0.005). In some patients, serum alkaline phosphatase values have remained elevated for more than 1 year, despite continued normality in thyroid variables. Before therapy, isoenzyme patterns analyzed by polyacrylamide gel electrophoresis were qualitatively normal. As therapy was instituted, the isoenzyme patterns changed markedly, with increased amounts of bone alkaline phosphatase appearing in the serum as T4 levels were declining and total alkaline phosphatase was rising. Thyroid tissue homogenates from patients with Graves' disease were found to have very low levels of alkaline phosphatase activity and an isoenzyme pattern quite distinct from that found in the serum.

Adolescent↗
PubMed1978

Serum thyrotropin releasing hormone (TRH)-degrading activity: a sensitive and rapid radiochemical assay procedure.

A rapid and sensitive method has been developed to assay thyrotropin releasing hormone (TRH)-degrading activity in serum. In this assay, the formation of proline, a major serum degradation product of TRH (pGlu-His-Pro-NH2), is measured. The procedure is based on the finding that proline can be readily separated from TRH with Dowex 50 by a batchwise procedure in a test tube.

Animals↗