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.