Increased STAT5 signaling in the ring dove brain in response to prolactin administration and spontaneous elevations in prolactin during the breeding cycle

Abstract

Prolactin acts on target cells in the central nervous system (CNS) to stimulate behavioral changes associated with parental care in birds, but the signaling mechanisms that mediate these actions have not been characterized. In mammals, the Janus Kinase 2-Signal Transducer and Activator of Transcription 5 (JAK2-STAT5) signaling pathway mediates many of the actions of prolactin. To assess the importance of this pathway in prolactin-sensitive target cells in the avian brain, we measured changes in activated (phosphorylated) STAT5 (pSTAT5) in the forebrain of female ring doves sampled as plasma prolactin levels change during the breeding cycle and in prolactintreated, non-breeding females. The anatomical distribution of cells exhibiting pSTAT5 immunoreactivity in dove brain closely paralleled the distribution of prolactin receptors in this species. The density of pSTAT5 immunoreactive (pSTAT5-ir) cells were highest in the preoptic area, the suprachiasmatic, paraventricular, ventromedial hypothalamic nuclei, the lateral and tuberal hypothalamic regions, the lateral bed nucleus of the stria terminalis, and the lateral septum. Mean pSTAT5-ir cell densities in these eight brain areas were several fold higher in breeding females during late incubation/early post-hatching when plasma prolactin levels have been observed to peak than in non-breeding females or breeding females sampled at earlier stages when prolactin titers have been reported to be lower. Similar differences were observed between prolactin-treated and vehicle-treated females in all three of the forebrain regions that were compared. We conclude that JAK2-STAT5 signaling is strongly activated in response to prolactin stimulation in the ring dove brain and could potentially mediate some of the centrally-mediated behavioral effects of this hormone.

Examining the disconnect between prolactin and parental care in avian brood parasites

“…Therefore, female cowbirds received subcutaneous implants for 7 days of prolactin treatment via osmotic minipumps (Azlet, model 1007D, DURECT Corp., Cupertino, California). Buntin and Buntin 54 showed prolactin‐dependent responses in the avian brain with these peripheral implants. Osmotic pumps contained either ovine prolactin (Sigma; St. Louis, Missouri; 3.3 μg/hr; 80 μg/day in 0.87% NaCl/0.01 M NaHCO 3 , 3:1 ratio v/v: 12 μL/day) or saline/bicarbonate vehicle alone.…”

“…Additional hypothalamic regions were similarly collected and collapsed into a single sample for RT‐qPCR. The hypothalamic regions collected were showed to possess labelling for pSTAT5 in nonoscine birds, 54 indicating prolactin receptor activity in these regions. Briefly, the Janus Kinase 2 (JAK2) ‐Signal Transducer and Activator of Transcription 5 (STAT5) pathway is a documented mediator of prolactin activity in mammals 61,62 and birds 54 and is used as a proxy for prolactin receptor activity.…”

“…Sample sizes for each species/treatment are as follows: brown‐headed cowbirds: N = 9 prolactin, N = 5 vehicle; bronzed cowbirds: N = 11 prolactin, N = 6 vehicle. Ovine prolactin was selected because it successfully elevated circulating prolactin levels in doves 54 . On day 8, females were rapidly decapitated, and brains were flash frozen on dry ice followed by −80°C storage until sectioning.…”

Identification of STAT3 and STAT5 proteins in the rat suprachiasmatic nucleus and the Day/Night difference in astrocytic STAT3 phosphorylation in response to lipopolysaccharide

“…STAT3 gene circadian oscillations have been reported in murine brown adipose tissue, and some signals of phospho‐ (p) STAT3 in the SCN have been mentioned in connection with leptin signaling in the hypothalamus (Ptitsyn and Gimble, ; Grosbellet et al, ). The only report of STAT5 in the SCN arose from studies of prolactin signaling in doves (Buntin and Buntin, ). Here we describe the presence of members of the Jak/STAT signaling pathway in the rat SCN and the proteins STAT3, ‐5A, and ‐5B.…”

Molecular genetic markers of economically important traits in dairy cattle

“…The family of STAT5 factors mediate the prolactin intracellular signaling pathway and activate the transcription of milk proteins upon cell exposure to prolactin [54]. In addition, STAT5 signals are transmitted to target genes through activation of growth hormone receptors [55].…”