Identification of Eya3 and TAC1 as Long-Day Signals in the Sheep Pituitary

Seasonally breeding mammals such as sheep use photoperiod, encoded by the nocturnal secretion of the pineal hormone melatonin, as a critical cue to drive hormone rhythms and synchronize reproduction to the most optimal time of year [1, 2]. Melatonin acts directly on the pars tuberalis (PT) of the pituitary, regulating expression of thyrotropin, which then relays messages back to the hypothalamus to control reproductive circuits [3, 4]. In addition, a second local intrapituitary circuit controls seasonal prolactin (PRL) release via one or more currently uncharacterized low-molecular-weight peptides, termed "tuberalins," of PT origin [5-7]. Studies in birds have identified the transcription factor Eya3 as the first molecular response activated by long photoperiod (LP) [8]. Using arrays and in situ hybridization studies, we demonstrate here that Eya3 is the strongest LP-activated gene in sheep, revealing a common photoperiodic molecular response in birds and mammals. We also demonstrate TAC1 (encoding the tachykinins substance P and neurokinin A) to be strongly activated by LP within the sheep PT. We show that these PRL secretagogues act on primary pituitary cells and thus are candidates for the elusive PT-expressed tuberalin seasonal hormone regulator.