Thyrotropin Releasing Hormone: Development of Inactivation System During Maturation of the Rat

A B S T R A C T To determine the role of thyrotropinreleasing hormone (TRH) in the regulation of thyroidstimulating hormone (TSH) secretion in the perinatal period, a physiological approach of neutralizing circulating TRH in the fetal andl early neonatal rat was employed. TRH-antiserum (TRH-AS) raised in rabbits and administered daily to low iodine-propylthiouracil (LID-PTU)-fed pregnant rats from days 12 to 19 of gestation markedly impaired the rise in serum TSH to LID-PTU when compared with normal rabbit serumtreated controls. In contrast, fetal serum TSH was unaffected by TRH-AS. The binding capacity of TRH-AS in the fetal serum (111 ng/iiil) far exceeded circulating TRH in the fetus. Similarly7, acute TRH-AS administration to the pregnant rat fed LID-PTU markedly decreased the serum TSH concentration in the mother, but not in the fetus, 60 niin after TRH-AS administration. Chronic TRH-AS administration to neonatal rats whose nursing mothers were fed LID-PTU was ineffective in decreasing the elevated serum TSH in the neonate through day 8 of life, whereas a slight but significant decrease in serum TSH was observed on day 10. Chronic daily TRH-AS administration to neonatal rats through day 10 of life had no effect on the later development of the hypothalamic-pituitary-thyroid axis. These findings suggest that TRH does not participate in TSH regulation during the perinatal life in the rat and that thyroid hormones are probably the main regulators of TSH secretion during this period.Placental TRH is niot importanit in regulating TSH secretion in the fetal rat. Furthermore, TRtH "deprivation" during neonatal life does not prevent normal later developmenit of the hypothalamic-pituitarythyroid axis.

Section: Methodsmentioning

confidence: 99%

Thyrotropin-Releasing Hormone is not Required for Thyrotropin Secretion in the Perinatal Rat

Theodoropoulos¹,

Braverman²,

Vagenakis³

1979

“…When a total pancreatectomy was performed on the 5th al of life of the rat, mean plasma TRH concentrations were significantly decreased 3 h afterwards (84.±9 vs. 63±7 pg/ml, P < 0.05). Neither the TRH concentrations in the brain, hypothalamus, or gastrointestinal tract, nor the pituitary-thyroid axis were affected by the pancreatectomy.This work was presented in part at the 62nd Annual Meeting of the Endocrine Society, Washington, D. C., 18-20 June 1980.Received for publication 21 July 1980 and in revised form 30 October 1980. 800 However, mean plasma TRH concentrations remained unaltered 3 h after removal of the hypothalamus and extrahypothalamic brain.…”

mentioning

confidence: 99%

Thyrotropin-releasing Hormone in the Systemic Circulation of the Neonatal Rat Is Derived from the Pancreas and Other Extraneural Tissues

Engler¹,

Scanlon²,

Jackson³

1981

A B S T R A C T Thyrotropin-releasing hormone immunoreactivity (IR-TRH) has been detected in the circulation ofthe neonatal rat. This immunoreactivity was demonstrated in purified ethanol extracts of plasma, and was indistinguishable from synthetic TRH using radioimmunoassay and chromatographic criteria. To determine the source of the circulating IR-TRH, tissue concentrations of TRH were analyzed during maturation of the rat. These studies revealed that during the first 10 d oflife, the pancreas contained the greatest concentration of IR-TRH of any organ (pancreas, 289±+35 pg/mg; hypothalamus, 13±3 pg/mg, day 5). Thereafter, pancreatic IR-TRH concentrations declined progressively while hypothalamic concentrations gradually increased (pancreas, 1.2±0.2 pg/mg; hypothalamus, 365±54 pg/mg, adult rat). IR-TRH was also found throughout the gastrointestinal tract but was not detected in the liver; spleen, kidney, or heart. IR-TRH from the pancreas and gastrointestinal tract gave radioimmunoassay binding displacement curves that were parallel to a curve generated with synthetic TRH, and co-migrated with synthetic TRH on Sephadex G-10 and high performance liquid chromatography. In addition, IR-TRH from purified pancreatic extracts was biologically active in that it released thyrotropin and prolactin from rat adenohypophysial cells maintained in monolayer culture. When a total pancreatectomy was performed on the 5th al of life of the rat, mean plasma TRH concentrations were significantly decreased 3 h afterwards (84.±9 vs. 63±7 pg/ml, P < 0.05). Neither the TRH concentrations in the brain, hypothalamus, or gastrointestinal tract, nor the pituitary-thyroid axis were affected by the pancreatectomy.This work was presented in part at the 62nd Annual Meeting of the Endocrine Society, Washington, D. C., 18-20 June 1980.Received for publication 21 July 1980 and in revised form 30 October 1980. 800 However, mean plasma TRH concentrations remained unaltered 3 h after removal of the hypothalamus and extrahypothalamic brain.From these results we conclude the following: (a) the TRH immunoreactivity in the circulation, pancreas, and gastrointestinal tract of the neonatal rat is indistinguishable from synthetic TRH; (b) pancreatic secretion provides a significant contribution to the IR-TRH in plasma, and a proportion of the circulating IR-TRH is derived from other extraneural sites. These findings therefore imply that alterations in hypothalamic and extrahypothalamic brain secretion of TRH are not reflected by changes in levels of this tripeptide in the systemic circulation.

“…For females, the rates of proline production were 2.12+0.90 in cord serum, 9.14+3.99 in euthyroid adult serum, and 3.19±+1.30 pmol proline/,ul/h in maternal serum (Table II). The differences between cord and euthyroid adult and between maternal and euthyroid adult are highly I TSH adult normal range = 0.2 to 3.5 AU/ml.…”

Section: Measurement Of Trh-degrading Activitymentioning

confidence: 96%

“…Duplicate samples were incubated at 37°C; 100 ,lI aliquots were withdrawn at 15, 30, 60, 90 and 120 min, diluted to I ml with the bovine serum albumin, NaCI, phosphate buffer, and the tubes were immediately placed into a boiling water bath for 3 min. The samples were then diluted further for TRH radioimmunoassay, which was conducted as previously described (9 (11). Strips were cut into 0.5-cm sections and transf'ere(d to counting vials.…”

Section: Measurement Of Trh-degrading Activitymentioning

confidence: 99%

See 1 more Smart Citation

Lower levels of thyrotropin-releasing hormone-degrading activity in human cord and in maternal sera than in the serum of euthyroid, nonpregnant adults.

Neary¹,

Nakamura²,

Davies³

et al. 1978

A B S T R A C T Thyrotropin-releasing hormone (TRH)-degrading activity was investigated in human cord, maternal, and euthyroid adult sera by measuring (a) the rate of disappearance of TRH and (b) the rate of formation of degradation products. The rate of TRH degradation in cord and maternal sera was 25-33% of that in euthyroid adult serum. Concomitantly, in cord and maternal sera, the rate offormation ofproline, a major TRH degradation product in serum, was one-quarter to onethird that in euthyroid adult sera. The differences were highly significant (P <0.001). The decreased levels of TRH-degrading activity in cord and maternal sera cannot be explained by (a) the presence of a dialyzable inhibitor, (b) the absence of an activator of TRH degradation, or (c) a reversal of the degradation process. There was no difference in the types of radioactive degradation products formed by cord, maternal, and euthyroid adult sera.The low level of TRH-degrading activity and its possible relationship to high thyrotropin-stimulating hormone levels in cord serum suggest that TRH-degrading activity may be a factor to consider in investigations of the perinatal pituitary-thyroid axis, but further studies are needed to determine the role of serum degradation of TRH in regulating physiological levels of TRH.