高泌乳素血症是一种血清泌乳素 (PRL) 升高的疾病。正常 PRL 水平分别是女性＜1087 pmol/L（25 µg/L 或 500 mU/L)，男性＜870 pmol/L （20 μg/L 或 400 mU/L）。[1]Casanueva FF, Molitch ME, Schlechte JA, et al. Guidelines of the Pituitary Society for the diagnosis and management of prolactinomas. Clin Endocrinol (Oxf). 2006 Aug;65(2):265-73.
https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2265.2006.02562.x
http://www.ncbi.nlm.nih.gov/pubmed/16886971?tool=bestpractice.com
[2]Serri O, Chik CL, Ur E, et al. Diagnosis and management of hyperprolactinemia. CMAJ. 2003 Sep 16;169(6):575-81.
http://www.cmaj.ca/content/169/6/575.long
http://www.ncbi.nlm.nih.gov/pubmed/12975226?tool=bestpractice.com
[3]Mah PM, Webster J. Hyperprolactinemia: etiology, diagnosis, and management. Semin Reprod Med. 2002 Nov;20(4):365-74.
http://www.ncbi.nlm.nih.gov/pubmed/12536359?tool=bestpractice.com
流行病学
高泌乳素血症是下丘脑垂体轴最常见的内分泌疾病。 高泌乳素血症的发病率为0.4%（正常成人人群中）~5%（在计划生育诊所就诊的人群中）。 闭经妇女中发病率增加到了9%，泌乳妇女中发病率为25%。 同时患有闭经和泌乳的女性中，70%患有高泌乳素血症。 患有不育或阳痿的男性中，高泌乳素血症发病率可达5%。[2]Serri O, Chik CL, Ur E, et al. Diagnosis and management of hyperprolactinemia. CMAJ. 2003 Sep 16;169(6):575-81.
http://www.cmaj.ca/content/169/6/575.long
http://www.ncbi.nlm.nih.gov/pubmed/12975226?tool=bestpractice.com
[3]Mah PM, Webster J. Hyperprolactinemia: etiology, diagnosis, and management. Semin Reprod Med. 2002 Nov;20(4):365-74.
http://www.ncbi.nlm.nih.gov/pubmed/12536359?tool=bestpractice.com
[4]Josimovich JB, Lavenhar MA, Devanesan MM, et al. Heterogeneous distribution of serum prolactin values in apparently healthy young women, and the effects of oral contraceptive medication. Fertil Steril. 1987 May;47(5):785-91.
http://www.ncbi.nlm.nih.gov/pubmed/3569555?tool=bestpractice.com
高泌乳素血症在儿童中比较少见。
病理生理学
PRL 是由 199 个氨基酸组成的多肽，由垂体前叶的泌乳素细胞分泌；循环中 80% 的 PRL 以 23 kD 的单体形式存在。PRL 二聚体（也被称为大 PRL）的分子量为 50 kD 到 60 kD，占 10%-15%；剩余的是巨泌乳素（也被称之为大-大 PRL），其分子量大（>150 kD），是 PRL 单体和 IgG 的复合物。[5]Ben-Jonathan N, LaPensee CR, LaPensee EW. What can we learn from rodents about prolactin in humans? Endocr Rev. 2008 Feb;29(1):1-41.
https://academic.oup.com/edrv/article/29/1/1/2354965
http://www.ncbi.nlm.nih.gov/pubmed/18057139?tool=bestpractice.com
[6]Gibney J, Smith TP, McKenna TJ. Clinical relevance of macroprolactin. Clin Endocrinol (Oxf). 2005 Jun;62(6):633-43.
https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2265.2005.02243.x
http://www.ncbi.nlm.nih.gov/pubmed/15943822?tool=bestpractice.com
许多垂体外组织也生成 PRL，这些组织包括不同的大脑区域、淋巴细胞、乳腺上皮细胞和肿瘤，以及子宫蜕膜、子宫肌层、泪腺、胸腺和脾脏。[7]Bole-Feysot C, Goffin V, Edery M, et al. Prolactin (PRL) and its receptor: actions, signal transduction pathways and phenotypes observed in PRL receptor knockout mice. Endocr Rev. 1998 Jun;19(3):225-68.
https://academic.oup.com/edrv/article/19/3/225/2530791
http://www.ncbi.nlm.nih.gov/pubmed/9626554?tool=bestpractice.com
尽管 PRL 与生长激素和人胎盘催乳素来源于共同的祖先激素，但它与这些激素在结构上没有共性。[5]Ben-Jonathan N, LaPensee CR, LaPensee EW. What can we learn from rodents about prolactin in humans? Endocr Rev. 2008 Feb;29(1):1-41.
https://academic.oup.com/edrv/article/29/1/1/2354965
http://www.ncbi.nlm.nih.gov/pubmed/18057139?tool=bestpractice.com
PRL 主要作用是刺激乳腺上皮细胞增殖，促进乳汁生成。PRL 除促泌乳作用外，还促进黄体形成和作用发挥，并抑制促性腺激素释放激素 (GnRH) 的脉冲式分泌。催乳素抑制 GnRH，将导致卵泡刺激素和黄体生成素水平降低。[7]Bole-Feysot C, Goffin V, Edery M, et al. Prolactin (PRL) and its receptor: actions, signal transduction pathways and phenotypes observed in PRL receptor knockout mice. Endocr Rev. 1998 Jun;19(3):225-68.
https://academic.oup.com/edrv/article/19/3/225/2530791
http://www.ncbi.nlm.nih.gov/pubmed/9626554?tool=bestpractice.com
此外，因为在睾丸支持细胞和间质细胞中存在催乳素受体，催乳素对精子发生和类固醇生成具有直接抑制作用。[8]Arowojolu AO, Akinloye O, Shittu OB. Serum and seminal plasma prolactin levels in male attenders of an infertility clinic in Ibadan. J Obstet Gynaecol. 2004 Apr;24(3):306-9.
http://www.ncbi.nlm.nih.gov/pubmed/15203635?tool=bestpractice.com
PRL 分泌呈脉冲式，主要受到下丘脑释放的多巴胺的抑制。多巴胺通过催乳素细胞上的 D2 受体发挥抑制作用。其他抑制因子还包括内皮素、肿瘤生长因子-β1（TGF-β1）和降钙素。[9]Kanyicska B, Lerant A, Freeman ME. Endothelin is an autocrine regulator of prolactin secretion. Endocrinology. 1998 Dec;139(12):5164-73.
https://academic.oup.com/endo/article/139/12/5164/2991322
http://www.ncbi.nlm.nih.gov/pubmed/9832457?tool=bestpractice.com
[10]Sarkar DK, Kim KH, Minami S. Transforming growth factor-beta 1 messenger RNA and protein expression in the pituitary gland: its action on prolactin secretion and lactotropic growth. Mol Endocrinol. 1992 Nov;6(11):1825-33.
http://www.ncbi.nlm.nih.gov/pubmed/1480172?tool=bestpractice.com
[11]Shah GV, Pedchenko V, Stanley S, et al. Calcitonin is a physiological inhibitor of prolactin secretion in ovariectomized female rats. Endocrinology. 1996 May;137(5):1814-22.
http://www.ncbi.nlm.nih.gov/pubmed/8612519?tool=bestpractice.com
雌二醇刺激泌乳素细胞增殖，使育龄女性（特别是孕妇）的泌乳素细胞数量增加。促甲状腺激素释放激素、血管活性肠肽和催产素也刺激 PRL 的生成。[5]Ben-Jonathan N, LaPensee CR, LaPensee EW. What can we learn from rodents about prolactin in humans? Endocr Rev. 2008 Feb;29(1):1-41.
https://academic.oup.com/edrv/article/29/1/1/2354965
http://www.ncbi.nlm.nih.gov/pubmed/18057139?tool=bestpractice.com
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