Dr. Grattan et al., Feedback regulation of PRL secretion is mediated by the transcription factor, signal transducer, and activator of transcription 5b, ENDOCRINOL, 142(9), 2001, pp. 3935-3940
PRL secretion from the anterior pituitary gland is inhibited by dopamine pr
oduced in the tuberoinfundibular dopamine neurons of the hypothalamus. The
activity of tuberoinfundibular dopamine neurons is stimulated by PRL; thus,
PRL regulates its own secretion by a negative feedback mechanism. PRL rece
ptors are expressed on tuberoinfundibular dopamine neurons, but the intrace
llular signaling pathway is not known. We have observed that mice with a di
srupted signal transducer and activator of transcription 5b gene have gross
ly elevated serum PRL concentrations. Despite this hyperprolactinemia, mRNA
levels and immunoreactivity of tyrosine hydroxylase, the key enzyme in dop
amine synthesis, were significantly lower in the tuberoinfundibular dopamin
e neurons of these signal transducer and activator of transcription 5b-defi
cient mice. Concentrations of the dopamine metabolite dihydroxyphenylacetic
acid in the median eminence were also significantly lower in signal transd
ucer and activator of transcription 5b-deficient mice than in wild-type mic
e. No changes were observed in nonhypothalamic dopaminergic neuronal popula
tions, indicating that the effects were selective to tuberoinfundibular dop
amine neurons. These data indicate that in the absence of signal transducer
and activator of transcription 5b, PRL signal transduction in tuberoinfund
ibular dopamine neurons is impaired, and they demonstrate that this transcr
iption factor plays an obligatory and nonredundant role in mediating the ne
gative feedback action of PRL on tuberoinfundibular dopamine neurons.