The physiological functions of progesterone (P4) in female reproductive organs including the mammary glands are mediated via the progesterone receptor (PR), but not all P4 functions can be explained by PR-mediated signaling. Progesterone receptor membrane component 1 (PGRMC1), a potential mediator of P4 actions, plays an important role in the ovary and uterus in maintaining female fertility and pregnancy, but its function in mammary glands has not been elucidated. This study investigated the role of PGRMC1 in mouse mammary gland development. Unlike in the uterus, exogenous estrogen (E2) and/or P4 did not alter PGRMC1 expression in the mammary gland, and Pgrmc1-knockout (KO) mice displayed reduced ductal elongation and side branching in response to hormone treatment. During pregnancy, PGRMC1 was expressed within both the luminal and basal epithelium and gradually increased with gestation and decreased rapidly after parturition. Moreover, although lactogenic capacity was normal after parturition, Pgrmc1 KO resulted in defective mammary gland development from puberty until midpregnancy, while the expression of PR and its target genes was not significantly different between wild-type and Pgrmc1-KO mammary gland. These data suggest that PGRMC1 is essential for mammary gland development during puberty and pregnancy in a PR-independent manner.

中文翻译：

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孕激素受体膜成分 1 是乳腺发育所必需的。

包括乳腺在内的女性生殖器官中孕酮 (P4) 的生理功能是通过孕酮受体 (PR) 介导的，但并非所有 P4 功能都可以通过 PR 介导的信号传导来解释。孕酮受体膜成分 1 (PGRMC1) 是 P4 作用的潜在介质，在卵巢和子宫中在维持女性生育能力和妊娠方面发挥重要作用，但其在乳腺中的功能尚未阐明。本研究调查了 PGRMC1 在小鼠乳腺发育中的作用。与子宫不同，外源性雌激素 (E2) 和/或 P4 不会改变乳腺中 PGRMC1 的表达，而Pgrmc1-knockout (KO) 小鼠对激素治疗的反应显示出降低的导管伸长和侧支。在妊娠期间，PGRMC1 在管腔和基底上皮中均有表达，并随着妊娠逐渐增加，分娩后迅速减少。此外，虽然分娩后泌乳能力正常，但Pgrmc1 KO 导致从青春期到妊娠中期的乳腺发育缺陷，而 PR 及其靶基因的表达在野生型和Pgrmc1 -KO 乳腺之间没有显着差异。这些数据表明 PGRMC1 对青春期和怀孕期间的乳腺发育是必不可少的，这种方式与 PR 无关。