Evidence of direct thyroid-stimulating action of thyrotropin-releasing hormone by perifusion of rat thyroid fragments.

The possibility that TRH has a direct thyroid-stimulating action has never been reported. A number of studies have shown a rise in serum concentrations of thyroid hormone after stimulation with TRH, without a rise in TSH secretion. This has led us to test TRH with rat thyroid fragment perifusion. Significant T4 release was observed for TRH concentrations as low as 1.7 X 10(-11) M. A dose-response curve was determined. The response was immediate, reaching a peak after the sixth minute and continuing for 15 min after the stimulation had ceased. This kinetic pattern is different from the one observed with TSH and with theophylline and suggests that a different mechanism may be involved. TRH seems to be capable of directly stimulating both the secretion of the pituitary hormone (TSH) and the corresponding peripheral gland, like LHRH, which also acts directly on the Leydig cells of the testis.

Sensitivity of thyrotropin (TSH) secretion to 3,5,3'-triiodothyronine and TSH-releasing hormone in rat during starvation.

The mechanisms by which plasma T3 and TSH decrease after a 3-day starvation period are not completely understood. In this study we tested the hypothesis of a possible modification in the sensitivity of thyrotroph cell to T3 and/or TRH. For that purpose, TRH tests were performed before and after a 3-day starvation in euthyroid, thyroidectomized, and T3-treated (75 or 175 ng/100 g BW) thyroidectomized male Wistar rats. TRH (10 to 500 ng/100 g BW) was injected iv through a chronically-implanted catheter. In another set of experiments, hypophyseal TSH content was also determined. Our results showed that after a 3-day-starvation plasma TSH decreased in all except hypothyroid rats; TSH responsiveness to TRH was unchanged in euthyroid rats but was increased in hypothyroid rats; and the T3-dependent increase in TSH responsiveness to TRH was significantly amplified. Moreover, there was a significant positive correlation between TSH responsiveness to TRH and hypophyseal TSH content. These results suggest that starvation induces an increased sensitivity of thyrotroph cell to T3.

Evidence of a thyrotropin-releasing hormone-dependent increase in plasma thyrotropin during refeeding of starved rats.

After 3 days of starvation, refeeding with carbohydrate (CHO) leads to a rapid increase in plasma T4 and T3, suggesting increased TSH secretion. The aim of the present study was to describe the time course of plasma TSH changes during refeeding with CHO and fat. Repetitive blood samples were obtained from freely moving animals by indwelling jugular venous catheters. Refeeding was performed on the fourth day of starvation at either 1100 or 1900 h, and blood was sampled during the preceding hour and during the following 3 h. In control experiments, blood was sampled over 4 h without refeeding. Refeeding with CHO and fat induced a significant increase in plasma TSH in the first hour. This increase could be abolished by a previous injection of an anti-TRH serum, while normal rabbit serum was without effect. Plasma corticosterone, measured hourly, also showed a tendency to increase with refeeding. It is concluded that refeeding of starved rats represents a reproducible stimulus for TSH secretion.

Use of the perifusion technique on rat thyroid fragments in the study of thyroid hormone secretion: short-term effects of thyrotrophin, theophylline and glucagon.

Perifusion of rat thyroid fragments was performed to study short-term effects of TSH, theophylline and glucagon on thyroid hormone secretion. This technique proved to be relatively convenient and sensitive, and gave reproducible results for at least 3 h, permitting precise kinetic studies of response to hormonal and pharmacological agents without any interference. There was a significant (P less than 0.001) linear correlation between the log TSH concentrations over the range 20-150 mu./ml and thyroid response. A second stimulation, using the same concentration of TSH, did not differ from the first stimulation if they were separated by an active 'washing' period of only 15 min. Theophylline also had a stimulating effect and like TSH induced an early release of the hormone fraction with a peak between 2 and 4 min, but it did not potentiate the TSH effect. Perifusion of rat thyroid fragments was found to be a useful tool for analysing dynamic effects of various substances. These effects were significant for periods of time as short as 20 min. Each thyroid preparation could be used a second time for another pharmacological or hormonal test. Our preliminary results also suggested that there was a direct glucagon effect on thyroid hormone secretion with a dose-response correlation.

Differential effects of passive immunization with somatostatin antiserum on adenohypophysial hormone secretions in starved rats.

The role of somatostatin (SRIF) on adenohypophysial hormone secretion in starved rats was reassessed by passive immunization. Because of the absence of pulsatile GH secretion in starved rats, the effects of the injection of SRIF antiserum on GH levels can be clearly demonstrated. To determine whether starvation modifies the sensitivity of the adenohypophysis to SRIF, we measured 125I-labelled iodo-N-Tyr-SRIF binding. There was no difference in the dissociation constant (Kd) nor in the maximal binding capacity (Bmax) in fed (n = 15) and starved (n = 15) animals (Kd = 0.38 +/- 0.09 (S.E.M.) and 0.45 +/- 0.09 nmol; Bmax = 204 +/- 39 and 205 +/- 30 fmol/mg protein respectively). Administration of SRIF antiserum resulted in a dose-dependent increase in plasma concentrations of GH, TSH and prolactin. The minimal effective dose of SRIF antiserum was 50 microliters for GH, 100 microliters TSH and 200 microliter for prolactin. Our results show that: starvation does not modify adenohypophysial SRIF-binding sites, in starved male rats endogenous SRIF exerts a negative control on prolactin secretion in vivo and sensitivity to endogenous SRIF seems to be different for each hypophysial cell type.

Isotopic test of capillary permeability to albumin in diabetic patients: effects of hypertension, microangiopathy, and duration of diabetes.

Capillary permeability to albumin (CPA) was studied by performing an isotopic noninvasive test with venous compression on 87 nonselected diabetics with no edema, no cardiac failure, and no peripheral vascular disease. Excessive albumin retention (AR greater than or equal to 8%) ten minutes after removal of the compression was found in 27 patients (31%). The radioactivity disappearance curve was then analyzed using the Fast Fourier Transform (FFT). An abnormal isotopic CPA test was thus found in at least 45 out of the 87 patients. The prevalence of an abnormal test was not different in type 1 and type 2 diabetics. We studied the independent effects of hypertension, presence of specific clinical signs of microangiopathy (retinopathy and/or significant proteinuria), and duration of diabetes. Among diabetics free of specific clinical signs of microangiopathy, the prevalence of an AR greater than or equal to 8% was significantly higher in those with hypertension (11/19) than in those with normal blood pressure (2/28) and in nondiabetic hypertensive patients (0/16). Among normotensive diabetics, the prevalence of an abnormal test was higher, but not significantly, in patients with specific clinical signs of microangiopathy (8/11) than in those free of them (7/18). Seven normotensive diabetics without specific clinical signs of microangiopathy had an abnormal test; five of them had had diabetes for more than five years. The prevalence of diabetes of more than five years duration was significantly higher in patients with an abnormal test (35/45) than in normotensive diabetics free of specific clinical signs of microangiopathy with a normal test (4/11).(ABSTRACT TRUNCATED AT 250 WORDS)

Increased capillary permeability to albumin and diabetic neuropathy.

An increase in the capillary permeability to albumin (CPA) has been reported in diabetic patients. We observed this frequently with a non-invasive isotopic test derived from the Landis method, using 99mTc-albumin and measuring residual radioactivity externally after removal of forearm venous compression. Evidence of the independent effects of hypertension and microangiopathy on CPA has already been found. The present work was designed to investigate CPA using the same test on diabetic patients without retinopathy and clinical proteinuria. Some of these patients had objective clinical distal and symmetrical polyneuropathy. Neuropathy was clearly present in 10 of the 11 patients with an abnormal test unexplained by causes other than diabetes and in only one of the 17 patients with a normal test. The most frequent abnormality affected the late radioactivity disappearance curve, which probably reflects an impaired lymphatic wash-out of interstitial albumin. These results strongly suggest a link between peripheral neuropathy and diabetic functional microangiopathy. An elevated blood flow secondary to sympathetic nerve failure may induce an increase in CPA and a saturation of lymphatic pumping which could also be deficient due to impaired lymphatic innervation.

Asymptomatic diabetic cardiomyopathy: a noninvasive study.

Forty-nine diabetic patients (26 type I and 23 type II), free of cardiovascular disease symptoms, were compared with 32 controls in a noninvasive study of left ventricular (LV) function. Absence of ischemic cardiopathy was confirmed by routine investigations and an exercise electrocardiogram using 12 leads with a thallium-201 myocardial scintigraphy. Diabetic patients had (1) a significantly prolonged mean isovolumetric relaxation time (IVRT) assessed by M-mode echocardiography and phonomechanography; (2) a significantly reduced E-F slope; (3) an increased mean Weissler index (pre-ejection period/LV ejection time). The IVRT and E-F slope abnormalities reflect increased myocardial stiffness and impaired LV compliance. The increased Weissler index reflects impaired myocardial contractility. These abnormalities were not related to sex, age, duration of diabetes or to the presence or extent of complications. No significant difference was found between diabetic patients and controls for mean diastolic and systolic LV diameters, thickness of the posterior wall or of the interventricular septum, assessed by echocardiography, or for the ejection fraction, determined by radionuclide angiocardiography. Finally, more than half of the patients with a frankly abnormal IVRT, Weissler index and E-F slope had had diabetes for less than 5 years, some even less than 2 years, without complications. These data show: (1) evidence of LV dysfunction specific to diabetes and unrelated to ischemic cardiopathy and hypertension; (2) the possible involvement of a metabolic factor in this early asymptomatic LV abnormality rather than microangiopathy.

[Microalbuminuria in diabetics with moderate hypertension]. / Microalbuminurie chez les diabétiques porteurs d'une hypertension artérielle modérée.

The relation between hypertension and diabetic nephropathy is complex. Nephropathy is probably involved in the elevated blood pressure found in diabetic patients. In maturity onset diabetes, patients may also have hypertension which is associated with obesity or essential hypertension. It has been suggested that in both types of diabetes, hypertension enhances the development of diabetic nephropathy. Moreover, an aggressive antihypertensive treatment seems able to reduce rate of decline in kidney function in insulin-dependent diabetic patients with patent nephropathy. In this work, creatinine clearance and microalbuminuria in 20 diabetic patients (mostly with maturity-onset-diabetes) with known moderate and effectively treated hypertension were therefore measured and the results were compared with those for 18 normotensive diabetic patients and 22 controls. Duration of diabetes was from one to 26 years (mean: 11 years) and duration of hypertension was from one to 35 years (mean: 10 years). Patients and controls had normal serum creatinine and proteinuria below 0.1 g/l. Microalbuminuria was measured by immunonephelometric assay using specific antiserum (sensitivity = 1.5 mg/l; intra and interassay coefficients: 6.5% and 8% respectively). The highest value was observed in hypertensive diabetic patients with retinopathy (group 1). But hypertensive patients without retinopathy (group 2) and normotensive patients also had significantly increased microalbuminuria. In group 1, microalbuminuria was significantly higher than in group 2. The creatinine clearance was reduced in groups 1 and 2 versus normotensive diabetics, but hypertensive patients were older.(ABSTRACT TRUNCATED AT 250 WORDS)

[Value of the study of plasma estrogens in the exploration of gynecomastia. Apropos of 48 cases]. / Intérêt de l'étude des oestrogènes plasmatiques dans l'exploration des gynécomasties.

Starting from 48 cases of gynecomastia, the authors report the following findings: -- Impairment of the testis function, as assessed by a low plasma level of testosterone, is rare. -- Basal values of gonadotropins are generally normal. -- Increased oestrogen urinary excretion and blood level are rarely found but, when present, they tend to decrease at successive evaluations. -- In six cases, plasmatic oestradiol can be suppressed by dexamethasone; although the small number of cases does not allow a definite conclusion, one might suggest a predominant adrenal source of plasmatic oestradiol.

[Quantitative aspects of iodine metabolism in one case of congenital iodotyrosine deiodinase defect (author's transl)]. / Aspects quantitatifs de la cinétique de l'iode dans un défaut d'iodotyrosine desiodase.

In a 27 years old patient an iodotyrosine deiodinase defect was responsible for a profound hypothyroidism (T4-RIA: indetectable -- TSH: 190 microU/ml) associated with a large goiter (about 300 g). MIT and DIT secretions were measured from the urinary cumulative specific activities, and the molar MIT/DIT ratio was 2.2. The thyroidal iodine exchangeable pool was as low as 177 micrograms. In two comparable patients rendered euthyroid by Lipodol injection, total thyroidal 127I pool was around 40 mg and the MIT/DIT ratio was degraded to 7 suggesting a mild biosynthetic defect by iodine excess.