Effect of neonatal treatment with monoclonal antibody to thyrotropin (TSH) receptor on the thyroxin (T4) level and certain parameters of the internal genital organs of adult rats.

Treatment of newborn rats with a single dose of monoclonal antibody to TSH receptor, caused permanent changes in the body weight, T4 level, and different sexual parameters. There are considerable sex and organ dependent differences in the sensitivity. Body weight and physical condition of males deteriorates, while the condition of the females is constant. However, T4 level of females significantly increases while that of the males does not change. The weight of seminal vesicle increases, while ovarian weight decreases. Effect of hCG treatment in adult age is inhibited by neonatal antibody (to TSH receptor) treatment. The experiment calls the attention to the imprinter effect of antibodies in the neonatal critical period, which effect could be manifested on the antibody's own (provoked) or foreign (related) receptor.

Changes in binding of monoclonal antibodies to TSH receptor following thyrotropin (TSH) and gonadotropin (GTH) pretreatments (studies on human thyroid and CHO cell lines).

Monoclonal antibody to TSH-receptor binds to the cells of human thyroid gland and to Chinese hamster ovary cell cultures. Pretreatments with TSH can decrease the binding of antibody, which effect is more expressed in CHO than in thyroid cells. Gonadotropin (FSH + LH) cannot influence the binding of antibody to thyroid, but there is an effect on CHO cells. Endotoxin (lipopolysaccharide, LPS) can depress the binding of antibodies on both objects and abolishes the difference between thyrotropin and gonadotropin receptors in their binding capacity, on both cell types. The experiments prove the similarity of thyrotropin and gonadotropin receptors which is responsible for the hormonal overlap.

Influence of experimentally induced endotoxemias on the thyroid function of rats.

The general membrane-damaging effect of endotoxins (LPS) may be also demonstrated on the follicular cells of thyroid gland. Serum T4 level significantly decreased and the response of thyroid gland to exogenous THS was markedly inhibited in experimental endotoxin and other so-called enteroendotoxemic shocks (e.g. intestinal ischemia, tourniquet shock, intestinal syndrome of radiation disease). A single subtoxic dose of LPS given to newborn rats decreased the T4 level, the response of thyroid to TSH in adulthood and caused a somatic retardation. The radio-detoxified endotoxin (TOLERIN) did not inhibit the thyroid response to TSH. TOLERIN pretreatment protected the rats against LPS and other enteroendotoxemic shocks.

Effect of gonadotropin (FSH-LH) and thyrotropin (TSH) treatment in adolescence on TSH-sensitivity in adult rats.

Hormonal imprinting is characteristic of the neonatal age, in which the receptor of the target cell matures, i.e. acquires its adult binding capacity, and cellular response becomes established in presence of the adequate hormone. The normal course of imprinting may be altered by certain molecules (related hormones, hormone analogons) which are able to bind to the receptor of the adequate hormone. The chemically related gonadotropic and thyrotropic hormones may overlap on each other's receptors not only in the perinatal age, but also in the early adulthood, and this overlap of the binding may give rise to an imprinting-like effect. An example of this phenomenon was observed in the present study, in which rats of seven weeks of age treated with gonadotropin showed a significant decrease in thyroidic response to TSH, and exposure to TSH failed to increase their basic thyroxine concentration to the normal (control) level. This depressive effect of gonadotropin was slightly reduced in the presence of LPS (endotoxin), causing membrane perturbation, while pretreatment with LPS and TSH accounted for an increased sensitivity to TSH in later phases of the rat's life. These experimental observations support the possibility of a special form of imprinting in adolescence.

Effect of gonadotropin (FSH + LH) and thyrotropin (TSH) administered with or without endotoxin at the age of three weeks on the response capacity of the thyroid gland in adult rats.

At the age of three weeks the experimental animals received either thyrotropin (TSH), or gonadotropin (FSH + LH), or endotoxin (LPS) alone or in combination. The effectivity of the treatments was evaluated at the age of two months (with or without further hormone treatment). Contrastingly to neonatal TSH treatment, TSH treatment at the age of three weeks did not give rise to imprinting. In female animals, however, TSH treatment increased the sensitivity to the related gonadotropin hormone. At the age of three weeks gonadotropin treatment--on its own--did not cause damages to the TSH receptors of the thyroid gland. While in previous experiments neonatal endotoxin treatment damaged considerably the thyroxin production of the adult thyroid gland, after treatments at the age of three weeks no similar effect could be observed. The treatment, however, decreased the sensitivity of the receptors to TSH. In female animals simultaneous administration of endotoxin and TSH led, even without further hormone treatment, to constant increase in T4 level (the increase could also be detected in the adult animal). Imprinting, however, did not develop. In male animals simultaneous administration of endotoxin and gonadotroph hormone decreased considerably the T4 baseline level, and further TSH or gonadotropin treatment was unable to enhance T4 production.

Presence (hPL, prostaglandin) and absence (triiodothyronine, thyroxine) of hormones in Tetrahymena: experimental facts and open questions.

The RIA technique detected prostaglandin (PGF2) and human placetal lactogen (hPL) in Tetrahymena cultures grown in bacto tryptone + yeast extract medium which, however, itself contained these hormones. About one to two per cent of the total hormone content of the medium was demonstrated intracellularly. Treatment with diiodotyrosine (T2), which is known to stimulate the growth of Tetrahymena, was followed by a decrease in the intracellular prostaglandin level. Triiodothyronine and thyroxine were not detected in Tetrahymena or in the medium, and did not appear in it on induction with TSH either. In the light of these observations it might well be doubted that prostaglandin was native in Tetrahymena: the use of synthetic media, and/or a reliable demonstration of the hormone content of the growth medium is recommended for evidence of hormone biosynthesis by unicellular organisms.

Effect of experimental shock conditions on the serum T4 level of rats and response of their thyroid gland to exogenous TSH.

150 min ligature of the superior (cranial) mesenteric artery (intestinal ischemia) significantly decreases serum T4 level and completely inhibits the response of the thyroid gland to exogenous TSH in rats. 300 min ligature of the hind limbs (tourniquet shock) decreases serum T4 level and the T4 response of thyroid gland to exogenous TSH in rats. The probable reasons for altered function of the thyroid gland in enteroendotoxemic shock conditions are discussed.

Effect of single neonatal melatonin treatment on in vitro thyroxin secretion and TSH or melatonin-modified cAMP level of one-month-old rats.

At the age of one month, incubation with melatonin of the thyroid glands of rats having received a single melatonin treatment at the age of three days resulted in increased thyroxine production. TSH was unable to enhance the thyroxine production of animals treated with melatonin neonatally, while its considerable increase could be observed in the case of control animals. Simultaneous TSH and melatonin treatment applied in vitro at the age of one month resulted in an approximately twofold increase of thyroid T4 production in rats having received neonatal melatonin treatment. In vitro alteration of the cyclic AMP level of the thyroid glands of intact and neonatally melatonin treated rats ran practically parallel, except that in the melatonin treated animals the cAMP level was higher after TSH administration. At the same time the cAMP level decreased in the thyroid gland of animals treated with TSH + melatonin. There was no exact correlation between the alterations of cAMP and T4 levels in the given experimental system.

Influence of hormonal imprinting on hormone level. Permanent receptor damaging effect of pituitary hormones administered to newly-hatched cockerels.

The overlapping effect of TSH and FSH on the gonad and on the thyroid gland can be demonstrated in cockerels even at the age of five weeks. These hormones influence the secretion of testosterone in a similar way and to a similar extent, while on the thyroxine level the influence of the specific hormone is more pronounced. Neonatal FSH and TSH treatment considerably decreased the basal testosterone level measured at the age of five weeks. Neonatal FSH treatment increased the basal T4 level while TSH treatment decreased it. The effect of TSH treatment administered at the age of five weeks in increasing the testosterone level was weakened after neonatal pretreatment with any iodine hormone. The effect of TSH treatment could only be inhibited by neonatal FSH pretreatment. Neonatal pretreatment with any of the trophormones caused a diminution of the T4 level augmenting of FSH and TSH administered at the age of five weeks.