Expression of the Parathyroid Hormone-Related Protein Gene in the Avian Oviduct: Potential Role as a Local Modulator of Vascular Smooth Muscle Tension and Shell Gland Motility during the Egg-Laying Cycle

Abstract

The phylogenetic conservation of the primary structure of PTH-related protein (PTHrP) supports an important, yet undetermined, role(s) for this molecule in the biology of birds and mammals. As an initial step toward understanding the function of PTHrP in birds, we investigated the expression of PTHrP mRNA in tissues of the egg-laying hen. This analysis revealed that PTHrP mRNA is expressed at various levels in lung, brain, heart, and tissues of the digestive tract, including the proventriculus (secretory stomach), gizzard, and small intestine. In the oviduct tissues of adult birds, PTHrP mRNA was detected in the isthmus (membrane-secreting) and shell gland (calcium-secreting) portions, but not in magnum (albumin secreting) tissue. During oviduct development, high levels of PTHrP mRNA present in the oviducts of the 12-week-old bird suggest a role for PTHrP in oviduct development. Interestingly, as the oviduct matures, relatively high levels of PTHrP mRNA segregate with the distal tissues that ultimately differentiate into the isthmus and shell gland (uterus). To address a possible role for PTHrP in the differentiated function of the shell gland, we followed the expression of PTHrP in the shell gland at different times in the laying cycle and found levels of PTHrP to transiently increase as the egg moves through the oviduct, gradually returning to basal levels in the 15-h calcification period. We localized the cycle-associated fluctuations in PTHrP mRNA levels to the shell gland serosa and smooth muscle layer. Immunoreactive PTHrP was localized to the serosal membrane as well as the smooth muscle layer of serosal arterioles, suggesting that PTHrP may modulate vascular smooth muscle activity. In support of this hypothesis, synthetic chicken PTHrP (1-34)NH2 was found to relax the resting tension of isolated shell gland blood vessels in a dose-dependent manner. Together, these data indicate that the expression of the PTHrP gene in the avian oviduct is both temporally and spatially regulated during the egg-laying cycle and that PTHrP may function as an autocrine/paracrine modulator of shell gland smooth muscle activity of both ductal and vascular origins. The vasorelaxant property of N-terminal fragments of PTHrP supports a role for this molecule in the temporal increase in blood flow to the shell gland during egg calcification.