Hypothyroidism Reduces Content and Increases in vitro Release of Pro-Thyrotropin-Releasing Hormone Peptides from the Median Eminence

Abstract

To determine the effect of thyroid status on proTRH-derived peptide processing and secretion, the content and release of TRH and prepro-TRH25-50 (PYE27), as well as somatostatin (SRIF) from median eminence (ME) or olfactory lobe (OL) tissue was studied in the rat. In hypothyroid animals treated by thyroidectomy (Tx), the ME content of TRH and PYE27 was reduced by more than 50%; further, when compared with euthyroid controls there was a significant 2-fold enhancement of the in vitro release of these peptides from ME fragments in response to depolarizing concentrations (60 mM) of potassium. Hyperthyroidism (T4 treatment) caused either no change or an increase in the ME content of these peptides and their response to K+ in vitro did not differ from control animals. The OL content of TRH and PYE27 was unaffected by thyroid status. SRIF levels in both ME and OL as well as in vitro secretion from the ME did not change with either Tx or T4 treatment. The ratio of TRH/PYE27 secretion throughout release and content studies remained stable at 3:1 to 4:1. These findings support the view that TRH in the hypothalamus but not OL is regulated by thyroid hormone. In this location hypothyroidism enhances not only pro TRH synthesis but also release of TRH and another proTRH-derived peptide. The consistent ratio of TRH/PYE27 suggests that regulation of TRH production by thyroid hormone occurs predominantly at the transcriptional level and not through posttranslation processing.