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

Abstract

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.

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

“…The first peak of IR-TRH described by these workers may therefore represent TRH bound to either lipid or protein. In addition, the presence of lipids or proteins in the radioimmunoassay could interfere with the binding of iodinated TRH with its antiserum, and result in higher levels ofTRH in blood compared with those reported here in plasma (19,20).…”

“…Several investigators have demonstrated the presence of low levels of TRH in the blood and plasma of the adult rat (16)(17)(18), and more recently, higher concentrations have been found in the blood of the fetal and neonatal rat (19,20). The reasons for the differences in the circulating levels of TRH at different periods of development of the rat have not been established.…”

“…Although the presence of TRH in the circulation of the neonatal and adult rat has been attributed to minute amounts entering the peripheral circulation from hypothalamic and extrahypothalamic brain sites (18,20), this hypothesis has not been established. These studies were therefore undertaken to determine the source of the TRH immunoreactivity (IR-TRH) in the circulation of the neonatal rat.…”

Pituitary Receptors during Development in the Rat. I. TRH Binding Capacity

“…Tonooka et al (21) reported that serum TSH concentrations in encephalectomized fetus was markedly elevated when pregnant rats were fed PTU and that hypothalamic lesions in these PTU-fed pregnant rats did not prevent the TSH rise in the fetus. Theodoropoulos et al (20) treated neonatal hypothyroid rats with TRH antiserum and found that this treatment was ineffective in decreasing serum TSH concentrations before the tenth day of life. We have recently observed that exogenous administration of TRH during the neonatal period leads to a significant increase in serum TSH concentration, which can be impaired in a dose-dependent fashion by treatment of the neonatal rat with T3 (22).…”

“…Theodoropoulos et al (20) recently presented data which suggest that TRH does not participate in TSH regulation during the first 10 days of postnatal life. Their results were primarily based on the lack of effect of TRH antiserum in suppressing fetal and neonatal TSH secretion.…”