Thiede M A, Harm S C, McKee R L, Grasser W A, Duong L T, Leach R M
Department of Bone Biology, Merck, Sharp, and Dohme Research Laboratories, West Point, Pennsylvania 19486.
Endocrinology. 1991 Oct;129(4):1958-66. doi: 10.1210/endo-129-4-1958.
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.
甲状旁腺激素相关蛋白（PTHrP）一级结构的系统发育保守性表明，该分子在鸟类和哺乳动物生物学中具有重要但尚未确定的作用。作为了解PTHrP在鸟类中功能的第一步，我们研究了产蛋母鸡组织中PTHrP mRNA的表达。该分析表明，PTHrP mRNA在肺、脑、心脏以及消化道组织（包括腺胃（分泌性胃）、肌胃和小肠）中以不同水平表达。在成年鸟类的输卵管组织中，在峡部（分泌膜）和壳腺（分泌钙）部分检测到PTHrP mRNA，但在膨大部（分泌白蛋白）组织中未检测到。在输卵管发育过程中，12周龄鸟类输卵管中存在的高水平PTHrP mRNA表明PTHrP在输卵管发育中起作用。有趣的是，随着输卵管成熟，相对高水平的PTHrP mRNA与最终分化为峡部和壳腺（子宫）的远端组织相关。为了研究PTHrP在壳腺分化功能中的可能作用，我们追踪了产蛋周期不同时间壳腺中PTHrP的表达，发现随着卵通过输卵管，PTHrP水平短暂升高，在15小时的钙化期逐渐恢复到基础水平。我们将PTHrP mRNA水平与周期相关的波动定位到壳腺浆膜和平滑肌层。免疫反应性PTHrP定位于浆膜以及浆膜小动脉的平滑肌层，表明PTHrP可能调节血管平滑肌活动。为支持这一假设，发现合成的鸡PTHrP（1 - 34）NH2以剂量依赖性方式松弛分离的壳腺血管的静息张力。总之，这些数据表明，在产蛋周期中，PTHrP基因在鸟类输卵管中的表达在时间和空间上均受到调节，并且PTHrP可能作为导管和血管来源的壳腺平滑肌活动的自分泌/旁分泌调节剂发挥作用。PTHrP N端片段的血管舒张特性支持该分子在卵钙化期间壳腺血流暂时增加中的作用。
