MULTIFACTORIAL MODULATION OF TRH METABOLISM

1. Thyrotropin releasing hormone (TRH), synthesized in the paraventric ular nucleus of the hypothalamus (PVN), is released in response to phy siological stimuli through median eminence nerve terminals to control thyrotropin or prolactin secretion from the pituitary. 2. Several even ts participate in the metabolism of this neuropeptide: regulation of T RH biosynthesis and release as well as modulation of its inactivation by the target cell. 3. Upon a physiological stimulus such as cold stre ss or suckling, TRH is released and levels of TRH mRNA increase in a f ast ard transient manner in the PVN; a concomitant increase in cfos is observed only with cold exposure. 4. Hypothalamic cell cultures incub ated with cAMP or phorbol esters show a rise in TRH mRNA levels; dexam ethasone produces a further increase at short incubation times. TRH mR NA are thus controlled by transsynaptic and hormonal influences. 5. On ce TRH is released, it is inactivated by a narrow specificity ectoenzy me, pyroglutamyl peptidase II (PPII). 6. In adenohypophysis, PPII is s ubject to stringent control: positive by thyroid hormones and negative by TRH; other hypothalamic factors such as dopamine and somatostatin also influence its activity. 7. These combined approaches suggest that TRH action is modulated in a coordinate fashion.