Dermatological Sciences, University of Manchester, Manchester Academic Health Science Centre, Manchester M6 8HD, UK.
Br J Dermatol. 2010 May;162(5):1127-31. doi: 10.1111/j.1365-2133.2010.09676.x. Epub 2010 Mar 10.
Human skin and scalp hair follicles are both a nonclassical target and an extrapituitary source of prolactin (PRL), which is a potent hair growth modulator. However, how the expression of PRL and PRL receptor (PRLR) is regulated in human skin is unknown.
To investigate whether two key stimulators of pituitary PRL secretion, thyrotropin-releasing hormone (TRH) and oestrogen, also regulate cutaneous PRL and PRLR expression.
Female scalp skin and/or microdissected hair follicles were treated for 6 days in serum-free organ culture with oestrogen (100 nmol L(-1)), TRH (1-10 ng mL(-1), 3-30 nm) or vehicle control. Quantitative immunohistomorphometry of skin and hair follicle sections was complemented with quantitative polymerase chain reaction for PRL and PRLR in cultured hair follicles and/or female human outer root sheath (ORS) keratinocytes.
Oestrogen treatment significantly upregulated PRL and PRLR immunoreactivity in selected skin and hair follicle compartments, at the gene and protein level (P < 0.05). TRH significantly increased PRL immunoreactivity and transcription in hair follicles (P < 0.05); however, while it also increased PRLR transcription in hair follicles, it downregulated PRLR immunoreactivity in the hair follicle ORS (P < 0.05).
Our pilot study shows that two key endocrine controls of pituitary PRL secretion, oestrogen and TRH, also regulate PRL and PRLR expression in human skin. This provides novel insights into the regulation of extrapituitary PRL and PRLR expression, and invites exploration of oestrogen and TRH as novel therapeutic agents in the management of skin and hair diseases characterized by aberrant PRLR-mediated signalling.
人类皮肤和头皮毛囊既是催乳素(PRL)的非经典靶标,也是垂体外的来源,而 PRL 是一种强有力的毛发生长调节剂。然而,目前尚不清楚 PRL 和 PRL 受体(PRLR)在人类皮肤中的表达是如何调控的。
研究垂体 PRL 分泌的两种关键刺激物——促甲状腺素释放激素(TRH)和雌激素是否也调节皮肤中的 PRL 和 PRLR 表达。
在无血清器官培养中,用雌激素(100nmol/L)、TRH(1-10ng/ml,3-30nm)或载体对照处理女性头皮皮肤和/或微分离的毛囊 6 天。用定量免疫组织形态计量学方法对皮肤和毛囊切片进行补充,并对培养的毛囊和/或女性人外根鞘(ORS)角质形成细胞中的 PRL 和 PRLR 进行定量聚合酶链反应。
雌激素处理显著上调了选定的皮肤和毛囊部位的 PRL 和 PRLR 免疫反应性,在基因和蛋白水平上均有上调(P<0.05)。TRH 显著增加了毛囊中的 PRL 免疫反应性和转录(P<0.05);然而,尽管它也增加了毛囊中的 PRLR 转录,但它下调了毛囊 ORS 中的 PRLR 免疫反应性(P<0.05)。
我们的初步研究表明,两种关键的垂体 PRL 分泌的内分泌调控物——雌激素和 TRH,也调节了人类皮肤中的 PRL 和 PRLR 表达。这为垂体外 PRL 和 PRLR 表达的调控提供了新的见解,并邀请探索雌激素和 TRH 作为治疗以异常 PRLR 介导的信号转导为特征的皮肤和毛发疾病的新型治疗剂。