Dose and time effects of treatment with low doses of a LRH agonist on testicular axis and accessory sex organs in rats.

LRH and its agonists have been shown to exert both stimulatory and inhibitory effects on testicular function. In the present study, the dose and length of treatment were tested to determine the appearance of the stimulatory and inhibitory effects of LRH agonist on testicular axis including the three levels. Two doses of an agonist of LRH, 40 and 100 ng/100 g body weight (buserelin, 'agonist'), were administered daily for 1 to 15 days to adult male rats. Control rats received the vehicle only. On day 1, 2, 4, 8 and 15 of treatment, the pituitary, testicular and peripheral levels (weight of accessory sex organs and androgen receptors in ventral prostate) were tested 6 h after the last injection. For the 15 days of treatment with both doses, a stimulatory effect of the 'agonist' was observed on LH and FSH release. A short exposure (1-2 days) to the low dose of the 'agonist' had a stimulatory effect on the density of LH/hCG testicular receptors (326 +/- 49 vs control 185 +/- 21 fmol/mg protein, mean +/- SEM), on the weights of seminal vesicles and ventral prostate and exposure to both doses led to high plasma testosterone levels (13.8 +/- 0.5 and 13.7 +/- 0.7 ng/ml, respectively, vs control 2.6 +/- 0.3 ng/ml), and to an increased density of nuclear androgen receptors in the ventral prostate (142 +/- 9 and 144 +/- 15 fmol/mg protein respectively vs control 97 +/- 12 fmol/mg protein).(ABSTRACT TRUNCATED AT 250 WORDS

Influence des oestrogènes sur la sensibilité de la réponse hypophysaire aux LHRH et TRH chez l'homme au cours de la vie [Influence of estrogens on pituitary responsiveness to LHRH and TRH in human (author's transl)].

Estrogens are supposed to be responsible for the increased sensitivity of the pituitary to LHRH and TRH observed in female in comparison to male adults. The influence of physiological and pharmacological variations of estrogens was studied throughout female life. Adolescents girls showed enhanced responses to both LHRH and TRH, as compared to cycling adult women. The adolescent pituitary seems to be particularly sensitive to the increasing estradiol secretion. Adult cycling women disclosed higher LH and FSH responses to LHRH during the periovulatory and luteal phases than during the follicular phase; prolactin response to TRH was enhanced only during the periovulatory phase while TSH response remained constant throughout the menstrual cycle. In adult women, sequential oral contraceptives increased LH, FSH and prolactin responses to LHRH and TRH while TSH response was unchanged. Combined contraceptives displayed an important inhibition of the LH, FSH and TSH responses but not of that of prolactin. The inhibitory effects on gonadotrophins and TSH may be due to the association of gestagens to estrogens. Postmenopausal women presented a TSH response to TRH similar to that found in male adults while prolactin response remained unchanged in spite of decreased basal values. The potentiatory effects of estrogens on the pituitary responsiveness to LHRH and TSH may be attributed either to an increased number or to an enhanced binding activity of the pituitary receptors to LHRH and TRH, as suggested by several experimental data

Abnormal iodoprotein distribution and resistance to proteolysis in Gunn rat black thyroid. An ultrastructural and biochemical study.

Gunn rats have a marked deficiency in hepatic UDP-glucuronosyl transferase activity which results in hyperthyroxinemia and hyperbilirubinemia. Their thyroids show a brownish-black discoloration associated ultrastructurally with intracellular dense granules and intraluminal dense masses. In order to determine whether colloid composition and colloid proteolysis are altered in the thyroid of the Gunn rat compared with the Wistar rat, we studied the in situ resistance of thyroid proteins to in vitro proteolysis, the pattern of in vivo (125I) labeled thyroid iodoproteins and the proteolysis of isolated iodoprotein fractions in both strains of rats. For the cytochemical study, thin sections of aldehyde-fixed and plastic-embedded thyroid tissue were treated with 0.3 or 1% pronase in aqueous solution. With the low concentration of pronase, the secretory granules in C-cells and the apical vesicles in follicular cells were extensively digested in both strains of rats, whereas the colloid in the follicular lumen and the colloid droplets were only partially digested. With the high concentration of pronase, the colloid in the lumen and the colloid droplets were more markedly digested in both strains. In the presence of both concentrations of pronase, the dense granules and intraluminal dense masses were unchanged in the Gunn rats. The (125I) iodoprotein pattern was investigated 24 h after a single injection of (125I) iodide and by labeling at the isotopic equilibrium. It was found that the (125I) thyroglobulin fraction was reduced, whereas the (125I) 3-8 S fraction was increased in Gunn rats compared to Wistar rats. Pronase hydrolysis of the soluble (125I) iodine fraction showed similar pronase-resistant fractions in both strains with the single labeling procedure. At the isotopic equilibrium, the pronase resistant fraction was significantly increased in Gunn rats (Gunn 24.0 +/- 5.3%; Wistar: 13.7 +/- 3.1% of the soluble 125I) and a linear correlation was observed between the (125I) 3-8 S fraction of the soluble extract and the pronase-resistant fraction. These data suggest that iodocompounds of small molecular size and low turnover accumulate in the thyroid of the Gunn rat due to their strong resistance to in vivo hydrolysis. A local accumulation of 3-8 S iodocompounds may occur within the intracellular dense granules and intraluminal dense masses in the thyroid of Gunn rat

Influence of sex and age on T3 receptors and T3 concentration in the pituitary gland of the rat: consequences on TSH secretion.

A reduced secretion of thyroid hormones with age has been documented in humans and animals with no substantial increase in TSH secretion, which may be indicative of an age-related impairment of the pituitary sensitivity to the negative control exerted by thyroid hormones. We have evaluated in rats the influence of sex and age on pituitary T3 nuclear receptors--known to be determinant in the regulation of TSH secretion--as well as on T3 concentration in the pituitary gland. As regards sex, the density of T3 receptors and the concentration of T3 in pituitary gland and plasma were greater in females than in males whereas pituitary and plasma TSH concentrations were less. As for age, the density of T3 receptors was greater in old male rats than in young ones with no changes in pituitary T3 and plasma TSH concentrations. In old female rats in contrast, there was no significant increase in T3 receptors but pituitary T3 was less and plasma TSH greater than in young female rats. In both sexes plasma thyroid hormones and pituitary TSH were reduced with age whereas TSH response to TRH was not altered. These results illustrate sex and age differences in pituitary T3 receptors and pituitary T3 concentration as well as in TSH secretion. In young animals of both sexes an inverse correlation is observed between the density of pituitary T3 receptors and plasma TSH. In contrast, in old animals the absence of this correlation is suggestive of an age-related impairment of T3 action on the thyrotrophs or of changes pertaining to other factors modulating TSH secretion

Relations between the selenium status and the low T3 syndrome after major trauma.

OBJECTIVE: Thyroxine (T4) is deiodinated to triiodothyronine (T3) by the hepatic type I iodothyronine deiodinase, a selenoprotein that is sensitive to selenium (Se) deficiency. After severe injury, T4 deiodination is decreased, leading to the low T3 syndrome. Injury increases free radical production, which inactivates the iodothyronine deiodinase. The aims were to study the Se status after major trauma and to investigate its relation to the low T3 syndrome. DESIGN: Preliminary prospective descriptive study. SETTING: Intensive care unit at a university teaching hospital. PATIENTS AND METHODS: 11 patients aged 41 +/- 4 years (mean +/- SEM), with severe multiple injuries (Injury Severity Score 29 +/- 2 points). A balance study was performed from day 1 to day 7. Serum and urine samples were collected from the time of admission until day 7, then on days 10, 15, 20, 25 and 30. Non-parametric tests and Pearson's correlation coefficients were used for analysis. RESULTS: Cumulated Se losses were 0.88 +/- 0.1 mumol/24h. Serum Se was decreased from admission to day 7. T3, free T3, and the T3/T4 ratio were low until day 5, being lowest on day 2; T4 and thyroid stimulating hormone were normal. Serum Se was correlated with T3 (r = 0.55, p = 0.0001), and with free T3 (r = 0.35). CONCLUSION: Se status is altered after trauma, with decreased Se serum levels upon admission to the ICU but with no major Se losses. Se is probably redistributed to the tissues. The correlation between Se and T3, along with the parallel decrease in T4 deiodination, indicates that reduced deiodination might be related to the transient decrease in serum Se

Pattern of plasma ACTH, hGH, and cortisol during menstrual cycle.

The pattern of secretion of plasma ACTH, hGH, TSH, LH, FSH and cortisol was studied in 12 menstrual cycles, representing 5 normal volunteers. Results were plotted by taking the LH-FSH midcycle peak as day 0. The typical menstrual cyclic LH and FSH pattern was observed in each case. ACTH, cortisol and hGH varied significantly throughout the menstrual cycle. ACTH was characterized by a decrease during the follicular phase, a nadir at day -2, followed by a significant increase to a peak at day 0, then a subsequent decrease and constant levels during the luteal phase until day +8. Cortisol was lowest in the follicular phase until day -4, and highest from day -2 to day 0. During the luteal phase, cortisol remained constant but was significantly higher than in the follicular phase (days -7 to -4). hGH showed a significant increase during the periovulatory period (days -3 to +3). No significant changes of plasma TSH were observed. These results suggest that pituitary hormones other than gonadotropins may be involved in the ovulatory mechanism, and reveal a degree of stimulation of the pituitary-adrenal axis without establishing whether the effect is direct or indirect