Maximal Increment Research Articles

Response to TRH, serum thyroid hormone concentration, and serum markers of autoimmunity after antithyroid therapy in Graves' disease.

In order to study the clinical significance of the TRH stimulation test the response to 200μg TRH given iv was studied in 33 patients with Graves’ disease from 3 to 70 months after discontinuation of antithyroid therapy. The relationship between the maximal increment in serum TSH and the level of thyroid hormones, the presence of circulating thyroid antibodies and the leucocyte migration inhibition, which is a measure of cellular hypersensitivity, was studied. In one group comprising 21 patients who had a normal response to TRH when tested 3 months after withdrawal of treatment or later in a few cases there was only one relapse which occurred within the first year after therapy; two patients who remained euthyroid had a temporary decrease of the response to subnormal levels (Δ TSH 30.0 mU/I) 2 1/2 and 3 years after therapy and this has remained abnormal although the patients are still euthyroid. The mean T4 and T3 and free hormone indices were significantly higher in the group of patients who had a subnormal response in comparison to the other group, although mostly the individual values were within the normal range. There was no correlation between the response and the circulating antibodies or migration inhibition. The results indicate that the TRH stimulation test has some although a limited value for the prediction of outcome after long-term antithyroid therapy. Absence of response may persist for several years without relapse and seems in some way to be related to the level of thyroid hormones in the blood, although mostly the individual values are within the normal range. No relationship exist, however, to common autoimmune parameters.

Mixed longitudinal data on skeletal age from a group of Dutch children living in Utrecht and surroundings

The height and weight of 1132 children, aged 8.0--17.0 years studied in 1970--72 in a semi-longitudinal survey in the Dental Institute of Utrecht, are compared with similar data from the national Dutch survey of 1965. Children measured in 1970--72 are somewhat taller than, but have the same weight as, those of the same ages in 1965. The increase in height since 1965 appears to be primarily due to the sub-group enrolled in vocational (as opposed to general) education. The maximal yearly increments in height and weight of the girls occurred between 11.0 and 12.0 years, and between 12.0 and 13.0 years, respectively. For boys the maximal increments in height and weight occurred between 14.0 and 15.0 years. Using the Tanner-Whitehouse 2 method, the skeletal age of this group of children was determined and compared with similar data from British standards. The results of the twenty-bone skeletal age indicated that Dutch boys, and to a lesser extent, girls, mature slightly later than English children at the approximate age range of 10.0--13.0 years and 8.0--10.0 years, respectively. After this age they follow roughly the growth curve of the British standards. The annual increment in skeletal age, plotted with chronological age as a time base, shows a peak for boys as well as girls that coincides with peak height velocity. The Carpal skeletal ages of boys and girls are almost identical in all age-groups with those of the British children, while the RUS skeletal age shows a much greater variability in the different age-groups. The variation in mean velocity (maturity points) between the two populations appears to be more marked in the RUS bones than in the round bones. The TW 1 skeletal age of each subject was plotted against the total TW 2, RUS or Carpal skeletal ages of the same individual. Equations are given for converting TW 1 skeletal ages into total TW 2 or RUS skeletal ages.

RESPONSE TO THYROTROPHIN‐RELEASING HORMONE AND TRIIODOTHYRONINE SUPPRESSIBILITY IN EUTHYROID MULTINODULAR GOITRE

In twenty-two female patients with euthyroid multinodular goitre of varying size, thyroid suppression of 131I thyroid uptake by triiodothyronine (T3) and thyrotrophin (TSH) release after thyrotrophin-releasing hormone (TRH) administration were compared with thyroid weight, estimated by a planimetric method, and with serum thyroxine (T4) and T3 concentrations. Maximal increment of TSH (deltaTSH) after TRH and per cent T3-suppressibility were inversely related to thyroid weight and not related to basal serum T4 or T3 concentrations. deltaTSH and per cent suppression correlated positively, but deltaTSH was more often subnormal than T3-suppressibility. A practical consequence of our study is that nonconformity of the two tests may occur. This should be kept in mind in the evaluation of patients with thyroid disorders.

The Bioavailability of Folic Acid Added to Wine

Folate deficiency is a frequent cause of anemia in alcoholics, but little attention has been paid to its prevention. Folic acid was readily soluble in wines of high ethanol content at concentrations of 10 microgram/ml. Lactobacillus casei folate activity of folic acid added to wines was well maintained during a month's storage at room temperature and fell to 61% to 66% of original activity after 3 months. Pteroylglutamic acid, 10 microgram/ml, added to wines and given in doses of the beverages (4 ml/kg body weight that caused inebriation, was well absorbed by six normal human volunteers (mean maximal increment in serum folate concentration +/- SEM, 71 +/- 8 ng/ml) and by seven recently intoxicated chronic alcoholics (mean increment, 94 +/- 4 ng/ml). Folate deficiency in alcoholics could be prevented by the fortification of alcoholic beverages with the vitamin.

Alteration of Large Intestinal Electrolyte Transport by Vasoactive Intestinal Polypeptide in the Rat

Vasoactive intestinal polypeptide (VIP) alters fluid and electrolyte movement in the small intestine. These studies were designed to evaluate the effect of VIP on Na and Cl transport across isolated large intestinal epithelia of the rat under short-circuited conditions since some evidence suggests that this intestinal hormone may not affect colonic ion transport. An increase in short circuit current and potential difference was produced by the addition of VIP to the serosal media at concentrations as low as 10-9 m , and maximal increments were observed at 10-7 m . In control mucosa JnetNa was 4.93 ± 0.52 μEq per hr ∙ cm2. The addition of VIP (6 × 10-7 m ) resulted in a decrease in JnetNa (0.87 ± 0.46 μEq per hr-cm2), a reversal of CI absorption to CI secretion (–2.42 + 1.12 μEq per hr • cm2), and an increase in short circuit current. Decreases in Jms were the predominant changes in unidirectional Na and Cl fluxes. The changes produced by VIP were identical with those induced by 10 mm theophylline. Furthermore, the effect of VIP plus theophylline on Jnft and short circuit current were undistinguishable from those of VIP alone and theophylline alone. VIP also increased mucosal cyclic AMP content. These studies indicate that VIP alters large intestinal ion transport; these changes are most likely mediated by increased mucosal levels of cyclic AMP.

EFFECTS OF CNS DOPAMINE AUGMENTATION ON STIMULATED PROLACTIN SECRETION12

The site, hypothalamic and/or pituitary, for dopaminergic inhibition of prolactin (PRL) secretion is unknown. Consequently, the effect of central dopamine (DA) augmentation on stimulated PRL release was determined in 5 healthy men. Regular insulin (o.1 U/kg i.v.), a potent central stimulus for PRL secretion, and TRH, a direct hypophyseal stimulus, were given alone or one hour after the third and fourth doses, respectively, of L-dopa plus the peripheral decarboxylase inhibitor, carbidopa (Sinemet 20/200 or 25/250 every 6 hours). PRL increased from 26.6 +/- 5.8 to 48.8 +/- 5.2 ng/ml (p less than 0.01) 40 minutes after insulin administration. In contrast, during Sinemet therapy the hypoglycemia-mediated PRL release did not occur, and the PRL levels were significantly lower than after insulin alone from 40 through 180 minutes. Following TRH, neither the maximal PRL rise (69.3 +/- 3.2, TRH alone vs 48.7 +/- 19.8 ng/ml, TRH + Sinemet) nor the maximal increment (37.5 +/- 5.5 vs 29.9 +/- 20.3 ng/ml) was significantly affected by Sinemet. It is concluded that central DA augmentation abolishes central but not peripherally mediated PRL release.

Hypothalamic endocrine dysfunction in anorexia nervosa.

ABSTRACT The hypothalamic-pituitary function of 21 women with anorexia nervosa, aged 15–34 years, was studied. The tests included, in addition to the usual tests of thyroid function, a TRH stimulation test with 200 μg of synthetic TRH given iv; the response of serum immunoreactive growth hormone to insulin; and the diurnal variation and response of plasma cortisol to insulin hypoglycaemia. The mean serum TSH level of the patients was higher than that of healthy controls. The mean maximal increment of TSH after TRH was similar in the patients and the controls. However, 18 of the patients but none of the controls showed a delayed TSH-response to TRH, i. e. the TSH-level at 60 min was higher than that recorded 20 min after TRH. Four of the patients had a low free thyroxine index, computed from the PBI and T3 Sephadex uptake values, and 3 of these were clinically hypothyroid. The means for PBI, T4 and the free thyroxine index were all significantly below the means for the controls. The basal serum growth hormone levels were increased in 9 out of 17 patients. In 4 of these an inadequate response to insulin or to glucagon was found. In 5 out of the 8 patients with normal basal growth hormone levels a normal response was found, whereas the remaining 3 showed a subnormal response. The serum growth hormone level was correlated with the degree of weight loss but not with the serum albumin concentration. Plasma cortisol at 08.00 was increased in 9 patients and the diurnal variation was inadequate in 6. Four patients showed a subnormal response to insulin-induced hypoglycaemia, and 2 out of 5 patients tested failed to show adequate suppression of plasma cortisol after 1 mg of dexamethasone. Dysfunction of the hypothalamic-pituitary axis is common in anorexia nervosa. A delayed TSH-response to TRH, compatible with hypothalamic dysfunction, seems to be an almost consistent feature of the disorder, and in some of the patients even clinical hypothalamic hypothyroidism may be evident.

Dose response to insulin in man: differential effects on glucose and ketone body regulation.

This prospective study was undertaken to elucidate the relationship between progressive log increments in plasma free insulin concentration and the resultant changes in the concentrations of plasma glucose, potassium, ketones, and free fatty acids in man. We attempted to define both the maximal and minimal threshold for substrate response relative to circulating concentrations of plasma insulin. Hyperglycemia and hyperketonemia were experimentally induced with dexamethasone in six diabetic subjects. Circulating plasma insulin concentration was acutely elevated by the continuous iv infusion of insulin in order to attain ten-fold increments in circulating plasma insulin concentration. Specifically, following a progressive elevation above basal concentration, maximal increments in circulating plasma insulin of 7 μU/ml, 90μU/ml, and 1, 621 μU/ml were obtained. The differential effects of these acute alterations in plasma insulin concentration on plasma substrate concentrations were compared to a controlsaline...

Apomorpine Inhibits the Prolactin but not the TSH Response to Thyrotropin Releasing Hormone1

Pretreatment of normal subjects with apomorphine, a dopamine receptor agonist, resulted in significant impairment of the subsequent prolactin (PRL) response to thyrotropin releasing hormone (TRH). The mean maximal increment of PRL was 27.9+/-2.4 ng/ml after TRH alone, and 11.9+/-3.0 ng/ml (P less than 0.001) after apomorphine plus TRH. In contrast, the.thyrotropin (TSH) response to TRH was unaffected by apomorphine (10.5+/-2.9 vs. 9.5+/-1.8 muU/ml, P greater than 0.5). These results demonstrate that dopaminergic effects are capable of inhibiting PRL responses to TRH, probably via a direct effect on the lactotrope cell. They also suggest that dopaminergic influences are not important in the regulation of TSH secretion.

Pharmacokinetics of hydrochlorothiazide in man.

Hydrochlorothiazide (hct) was administered orally in four different doses (12.5, 25, 50 and 75 mg), to eight healthy volunteers. Plasma and urine concentrations of hct were determined by GLC. Maximal plasma levels were found at 1.5–5 h, and averaged 70, 142, 260 and 376 ng × ml−1 respectively. The peak plasma levels and AUC0→9h of hct were highly correlated (p<0.001) with the dose. The decline in the plasma curve was biphasic in those experiments in which the plasma levels of hct could be determined for at least 24 h. The half life of the slower phase lay between 5.6 and 14.8 h. The urinary recovery of hct, which represented the gastrointestinal absorption, averaged 65 to 72 per cent of the dose. The mean renal plasma clearance did not vary with the dose and averaged 319 to 345 ml × min−1. The diuresis during the 10 h after hct 12.5 mg exceeded that after placebo by a mean of 800 ml. The diureses was not increased further after higher doses of hct. The maximal natriuretic effect (+ 100 mmol), too, was found after the 12.5 mg dose. The excretion of potassium, however, rose with increasing doses; the maximal increment, after 75 mg hct, averaged 25 mmol. The excretion of calcium was significantly increased after 50 mg hct (+ 0.6 mmol). The maximal effect on magnesium excretion occurred after 25 mg hct (+ 0.5 mmol). In healthy volunteers there was no correlation between peak plasma level of hct or AUC0→9h and the renal excretion of water and electrolytes.

Specific and Nonspecific Multiple Unit Activities During the Onset of Pentylenetetrazol Seizures. II. Acute Lesions Interrupting Nonspecific System Connections

Nonspecific cortical, thalamic, mesencephalic, and pontine multiple unit activities (MUA) and changes in EEG and MUS of the sciatic nerve after threshold pentylenetetrazol activation were studied in three groups of animals in which neuronal connections were interrupted at three different levels of the central nervous system: spinal, mesencephalic, and prethalamic. Maximal increments of nonspecific MUA and maximal increments and maximal decrements of sciatic MUA after pentylenetetrazol from each group of lesioned animals were statistically compared with tose observed in intact animals. 1. Pentylenetetrazol threshold for producing cortical tonic-clonic EEG discharges was increased in animals with nesencephaic and prethalamic lesions but was not modified in animals with spinal transection. 2. Cortical MUA maximal increment was significantly decreased in mesencephalic and prethalamic lesioned animals, whereas thalamic MUA maximal increment was significantly decreased in mesencephalic and significantly increased in prethalamic lesioned animals. Pontine MUA maximal increment was significantly increased in spinal, mesencephalic, and prethalamic lesioned animals, and mesencephalic M-A maximal increment was not significantly modified in either prethalamic lesioned or in spinal transected animals. 3. Sciatic MUA maximal increment and maximal decrement were significatly decreased in spinal transected animals, whereas only maximal increment was significantly decreased in mesencephalic and only maximal decrement was significantly decreased in prethalamic lesioned animals. These results based on lesion experiments permit us to infer than under normal cinditions the development of generalized seizures induced by threshold pentylenetetrazol injection is highly dependent upon the neuronal interactions between nonspecific structures at different levels of the central nervous system. The possible nature of these neuronal interactions in the intact animals is discussed.

33: Circadian variation: 30 diurnal patterns of plasma progesterones determined every 60min. in children with CAH

In untreated congenital adrenal hyperplasia (CAH) the plasma levels of glucocorticoid precursors progesterone (P) and 17-Hydroxy-Progesterone (17-OHP) are elevated. Few investigations suggest circadian variations of these. But two factors remain uncertain: first the time of maximal peaks which may be important for timing of replacement therapy and second to what extent therapy has to suppress circadian variations. To elucidate this we estimated plasma progesterones in 60 min. intervalls over a period of 24 hours. The method as reported previously, does not differentiate between P and 17-OHP. 13 untreated patients showed circadian variations as known for cortisol: the lowest values were noticed at 7 p.m. (51±14 ng/ml, range:6-156), the highest at 4 a.m. (202±26 ng/ml, range:78-379). In 7 untreated patients dexamethasone (2 mg/d) caused a marked decrease of plasma levels within a few hours. Circadian variations were abolished and plasma levels at 7 p.m. (8±1 ng/ml, range: 4-13) and 4 a.m. (10±2 ng/ml, range:6-21) were low. 10 patients treated with 25 mg/m2/d hydrocortisone revealed suppressed but still visible diurnal patterns with a maximal increment at 7 a.m. (88±20 ng/ml, range:26-226). Trials of different dosage and timing of replacement therapy failed to have a convincing effect on flattening the circadian curves. Current replacement therapy obviously does not cause complete suppression. This possibly is brought about by overdosage only. Growth under usual therapy might be related to the average hight of the circadian curves. Supported by Deutsche Forschungsgemeinschaft, SFB 34

Dissociation between TSH and prolactin dynamics in treated thyrotoxicosis.

TSH and prolactin secretory patterns in thyroid disease have generally been reported as concordant. We studied TSH and prolactin responses to TRH infusion (500 mug) in euthyroid individuals previously treated for thyrotoxicosis with 131I or antithyroid drugs. The 131I-treated group (seven men, twenty women) had been clinically and biochemically euthyroid (normal serum thyroxine and triiodothyronine levels) for 6 months to 4-5 years (kappa +/- SD = 17-1 +/- 4-1 months). Based on maximal TSH increment (deltaTSH), three patient groups were identified: Group 1 [normal deltaTSH, n = 6]: delta prolactin was normal in two, blunted in one and exaggerated in three. Group 2 (exaggerated TSH response, n = 8): delta prolactin was normal in two, blunted in one and exaggerated in five. Group 3 (TSH nonresponders, n = 13): delta prolactin was normal in five, blunted in three, and exaggerated in five. Eleven patients (three men, eight women) were studied after 6 months antithyroid-drug treatment. All were clinically and biochemically euthyroid. All but one showed a blunted TRH-TSH response. All three men showed an exaggerated delta prolactin as did four of eight women. Three women showed a blunted delta prolactin and in one, delta prolactin was normal. Thus, TRH-induced TSH and prolactin response patterns in treated thyrotoxicosis are not uniformly concordant, and, while a blunted or absent TSH response commonly persists long after euthyroidism has been restored, this is most frequently accompanied by a normal or exaggerated prolactin response.

Prolactin and thyrotropin responses to thyrotropin-releasing hormone in patients with secondary amenorrhea: the effect of bromocriptine.

Prolactin (PRL) and thyrotropin (TSH) responses to a 200 mug intravenous thyrotropin-releasing hormone (TRH) bolus were measured by radioimmunoassay in 11 women with hyperprolactinemic amenorrhea and 9 with normoprolactinemic amenorrhea. In all cases, the tests were carried out under basal conditions and repeated during bromocriptine treatment. In women whose basal PRL level was normal; TRH caused a maximal PRL increment of 85 +/- 25.2 mug/l (mean +/- SE), while those women whose basal PRL level was raised showed a smaller increase (5.2 +/- 11.9 mug/l) (P=0.02). The peak levels were not significantly different in these two groups (95.0 +/- 26.7 and 134.6 +/- 35.9 mug/l) (P is greater than 0.1). During bromocriptine treatment, the raised PRL levels decreased in all cases, but levels over 30 mug/l remained in 3 patients, one of whom turned out to have a pituitary tumor. Prolactin responses to TRH were markedly inhibited in normoprolactinemic patients by the dose of bromocriptine used. The mean maximal net increase of PRL was 2.0 +/- 0.9 mug/l in normoprolactinemic patients and 11.0 +/- 8.1 mug/l in hyperprolactinemic patients taking bromocriptine. After TRH stimulation during bromocriptine, the peak PRL levels in hyperprolactinemic patients were higher (32.7 +/- 10.5 mug/l) than in normoprolactinemic patients (7.2 +/- 1.5 mug/l). Unlike what has been described for hypothyroid patients, the basal TSH level in euthyroid amenorrhea patients was not affected by bromocriptine, and we found that bromocriptine has no effect on the TRH-TSH response.

The pituitary response to exogenous luteinizing hormone releasing factor in steroid-treated gonadectomized rats.

Rats gonadectomized 1-2 months previously were anaesthetized with sodium pentobarbitone and 50 ng/100 g body weight of a synthetic decapeptide gonadotrophin releasing factor (LH-RF) injected intravenously. Palsma concentrations of LH and FSH were determined by radioimmunoassay in samples taken before and at intervals up to 60 min after injection of LH-RF. The pituitary response was evaluated by determining the maximal increment in plasma gonadotrophin concentrations and by estimating the area under the plasma gonadotrophin concentration curves. In both males and females the pituitary response was increased in animals given 20 mug oestradiol benzoate 3 days earlier. Progesterone (2-5 mg) had no effect on the response measured 4 h later in oil-treated rats, male or female. In oestrogen-primed rats progesterone administration produced a significantly increased response in females that was not seen if sodium pentobarbitone was given at the time of progesterone injection. In oestrogen-primed males progesterone produced some increase in sensitivity but less than was seen in females. Both in males and in females that had received androgen on day 4 of postnatal life sodium pentobarbitone had no effect on the responses of oestrogen plus progesterone-treated rats to LH-RF. When two injections of LH-RF were given 60 min apart, the second response was greater than the first in animals, both male and female, that had been primed with oestrogen. The second response was no greater than the first in oil-treated females. The results suggest that oestrogen can increase pituitary sensitivity of LH-RF in both male and female rats and that LH-RF itself can increase pituitary sensitivity to a second injection of LH-RF in both male and female rats if they have received oestrogen. It is suggested that the differences between the pituitary responses of females and males after oestrogen plus progesterone treatment and the major differences in gonadotrophin secretion reported previously (Brown-Grant, 1974) may be accounted for on the basis of there being a relatively slight increase in endogenous LH-RF secretion with a consequent marked rise in pituitary responsiveness in female but not in male rats.

A study on serum luteinizing hormone response to luteinizing hormone-releasing hormone iny hyper- and hypothyroidism (author's transl)

In order to study the mechanism of gonadal dysfunction in patients with abnormal thyroid function, the pituitary luteinizing hormone (LH) response to 200 mug of luteinizing hormone-releasing hormone (LH-RH) was investigated in 20 untreated and 18 treated hyperthyroid patients and in 21 untreated and 8 treated hypothyroid patients in addition to 29 matched control subjects. Serum LH levels were measured by double-antibody radioimmunoassay technique with HLH kit Daiichi. In untreated hyperthyroid men, the slightly elevated mean basal level and the exaggerated mean response to LH-RH of LH were observed, and in treated hyperthyroid men, both values were found to be similar to those of matched control men. Furthermore, in these patients, the maximal increments and the net increments of responses to LH-RH of LH were correlated with serum thyroxine levels and Thyopac-3 values. In most untreated and treated hyperthyroid premenopausal women with and without menstrual disturbances, the basal levels and the responses to LH-RH of LH were similar to those of matched control premenopausal women. In untreated hyperthyroid postmenopausal women, the mean basal level of LH was elevated, although the mean LH response to LH-RH was similar to that of matched control postmenopausal women, and in treated hyperthyroid postmenopausal women, the mean basal level and the mean response to LH-RH of LH were similar to those of matched control postmenopausal women. Furthermore, in these patients, the basal levels were correlated with serum thyroxine levels. In untreated and treated hypothyroid men, the mean basal level and the mean response to LH-RH of LH were similar to those of untreated and treated hyperthyroid postmenopausal women. In most untreated and treated hypothyroid premenopausal women with and without menstrual disturbances, the basal levels were observed to be inconsistent, and the LH responses to LH-RH were similar to those of matched control premenopausal women. In untreated and treated hypothyroid postmenopausal women, the mean basal level and the mean response to LH-RH of LH were similar to those of matched control postmenopausal women. These data indicate that the ability of the pituitary to secrete LH in patients with abnormal thyroid function was augmented in hyper- and hypothyroid men, and augmented in hyper-, but normal in hypothyroid postmenopausal women. Therefore, it is concluded that the cause of gonadal dysfunction at least in the premenopausal women with abnormal thyroid function lies not inside but outside the pituitary gland.

Development of taylor instability in compressible conducting media in a magnetic field

Article [1] is devoted to the investigation of the interface of viscous incompressible conducting media in the presence of a current and with a magnetic field with a small magnetic Reynolds number. Article [2] discusses the stability of a contact discontinuity in compressible media. In this article, in an analysis of the case of long-wave vibrations in the region z<0, the boundary condition is unsatisfactorily met. Therefore, in this part of it the author actually considered a problem with a mass force f=(0, 0, −g sign z) instead of f=(0, 0, −g). The present, article considers the stability of the interface of compressible conducting media in a magnetic field. It is postulated that the magnetic intensity can undergo a discontinuity at this boundary. The article gives the dependence of the maximal increment of the rise in the instability on the determining parameters. An analysis is made of the stability of a contact discontinuity as a function of the angles formed by the wave vector and the intensity of the magnetic field. The stabilizing effect of the walls on the stability is demonstrated.

A radioimmunoassay for serum rat thyroglobulin. Physiologic and pharmacological studies.

A double antibody radioimmunoassay has been developed to measure thyroglobulin in rat (RTg) serum. The lowest detectable quantity measurable was 5.0 ng/ml. Specificity was documented by: (a) fall in serum RTg to undetectable levels after thyroid ablation; (b) the fact that L-thyroxine, D-thyroxine, L-triiodothyronine, D-triiodothyronine, triiodothyroacetic acid, tetraiodothyroacetic acid, triiodothyropropionic acid, moniodotyrosine, diiodotyrosine, and human thyroglobulin (HTg) in concentrations up to 40,000 ng per tube did not cross-react in the assay; (c) the demonstration that constant levels of serum RTg were observed while varying amounts of serum (criterion of parallelism) were introduced in the assay. The mean RTg concentration in tail vein blood of adult Sprague-Dawley rats were 101.5 +/- 13.0 ng/ml (SEM) (n=21); values ranged from 12.0 to 258.0 ng/ml. Chronic administration of a high-iodine diet (HID) did not affect serum thyroglobulin levels. Chronic administration of a low-iodine diet (LID) and propylthiouracil (PTU) led to a statistically significant increase in serum RTg that was accompanied by a significant rise in serum thyrotropin (rTSH). Serum thyroxine (T4) administered to normal rats for 14 days (20 mug/day subcutaneously) depressed serum RTg concentration from a mean level of 119.4 +/- 17.5 ng/ml (n=19) to a mean of 35.0 +/- 0.27 ng/ml (n=19) (P less than 0.001). While rats were on continuous T4 suppression, bovine thyroid-stimulating hormone (bTSH) given intravenously (2 IU) resulted in a mean maximal increment of RTg of 332.0 +/- 81.5 ng/ml (n=6) at 24 h. IgC-(LATS) long-acting thyroid stimulatory injected intravenously resulted in a mean maximal increment of RTg concentration at 96 h of 87.2 +/- 14.3 ng/ml (n=5). Normal IgG had no statistical significant effect of RTg levels at any time after the injection.

THE RESPONSIVENESS OF THE ANTERIOR PITUITARY GLAND TO LUTEINIZING HORMONE RELEASING FACTOR IN RATS EXPOSED TO CONSTANT LIGHT

The responsiveness of the anterior pituitary gland to synthetic luteinizing hormone releasing factor (LH-RF) was tested in rats exposed to constant light. At a dosage of 50 ng LH-RF/100 g body wt the mean maximal increments in plasma LH and FSH were similar to those at 10.00 h of pro-oestrus. The increments in the plasma gonadotrophins at dosages of 500 and 1000 ng LH-RF/100 g body wt did not differ significantly from those at 250 ng LH-RF/100 g body wt. These findings suggest that, in contrast to rats which exhibit regular oestrous cycles, the preovulatory (post-coital) release of LH in rats exposed to constant light may depend almost entirely on the release of a relatively large amount of LH-RF into hypophysial portal vessel blood. Whereas in pro-oestrous animals a relatively small fraction of the readily releasable pool of LH is released during the spontaneous preovulatory surge, in rats exposed to constant light most releasable LH appears to be discharged during the reflex preovulatory surge of this hormone. The concentrations of radioimmunoassayable FSH in blood samples withdrawn before the injection of LH-RF support the view that FSH secretion in the rat is increased by constant exposure to light.

EFFECT OF ORAL THYROTROPHIN‐RELEASING HORMONE ON SERUM THYROXINE IN GROWTH HORMONE DEFICIENT AND NORMAL CHILDREN

Oral administration of synthetic TRH in a dose of 80 mg/1-73 m-2 at 0 and 12 h to normal and constitutionally small children caused a significant increase of total serum thyroxine (T4) within 6-24 h. The mean maximal T4 increment was +3-7 plus or minus 1-1 and +3-8 plus or minus 1-2 mug/dl (mean plus or minus 1 SD) respectively in the two groups. Of seventeen euthyroid GH deficient children, fifteen showed a normal and two patients a slightly subnormal response. Of fifteen hypothyroid GH deficient children nine had a prompt and normal increase of serum T4 indicating primary TRH deficiency. Two had a delayed T4 response and four had no response, even after prolonged stimulation. The localization of the primary defect in these latter subjects with severe hypothyroidism can not be made by measuring T4 only, since the thyroid gland may become unresponsive to TSH after longstanding TSH deficiency. TSH measurements are necessary in these circumstances for a clear localization of the primary defect. One GH deficient patient with hypothalamic TRH deficiency was treated with high oral TRH doses for 7 months and showed no side effects.