DEVELOPMENTAL BIOCHEMISTRY AND PHARMACOLOGY OF RAT PITUITARY THYROTROPIN-RELEASING HORMONE RECEPTOR
Thyrotropin-releasing hormone (TRH, pGlu-His ProNH(,2)) is a hypothalamic hypophysiotropic hormone known to produce a number of unique effects on the central nervous system in addition to its ability to release thyrotropin (TSH) and prolactin from adenohypophysis. The mechanism by which TRH elicits TSH release is not fully understood. However, a number of observations from various laboratories suggest that a receptor for TRH on the anterior pituitary may play an important role in this process. The studies presented in this dissertation deal with the biochemistry and pharmacology of the TRH-receptor in relation to TSH secretion. The down regulation of TRH-receptor by TRH in rats was studied by measuring the changing receptor density following TRH administration for various periods. The TRH-receptor concentration was determined by incubating crude pituitary membrane preparations with ('3)H-TRH in the presence or absence of a large excess of non-radioactive TRH. The bound ('3)H-TRH was separated from free ('3)H-TRH by filtration through GB/B filters. The data show that TRH indeed regulates the number of its own receptors like many other hormones. This regulatory role of TRH was found to be mediated directly by TRH and not TSH or T(,3). The measurement of the ontogenetic development of TRH-receptor in male as well as female rats showed that neonatal rats possess a much higher number of TRH-receptors compared to adults. This observation now can partly explain the biochemical and endocrine basis for exaggerated TSH-response to exogenous TRH administration in neonates compared to adult rats.