Tan K S, McFarlane L C, Lipworth B J
Department of Clinical Pharmacology, Ninewells Hospital & Medical School, University of Dundee, UK.
Eur J Clin Pharmacol. 1997;52(4):281-3. doi: 10.1007/s002280050290.
We have previously demonstrated that exogenous progesterone, but not oestrogen, upregulated lymphocyte beta 2-adrenoceptors (beta 2-AR) when given during the follicular phase in healthy females. In the present study, we were interested to see whether this facilitatory effect of female sex-steroid hormones could be demonstrated in healthy males.
Nine healthy male volunteers with a mean age of 24 years completed this randomised, double-blind, placebo-controlled, cross-over study. They were randomised to receive either oral placebo, oestradiol valerate (4 mg) or medroxyprogesterone (40 mg). The study medication was given in two divided doses 12 h apart. Subjects attended the laboratory at baseline (T0 is baseline), 1 h after ingestion of the second dose of study medication (T1) and 24 h later (T24). At each visit, 60 ml of peripheral blood was withdrawn for measurement of serum oestradiol, progesterone and testosterone levels, and for lymphocyte beta 2-AR parameters; density (Bmax), binding affinity (Kd) and maximal cyclic AMP response to isoprenaline (Emax).
Baseline levels of sex-steroid hormones were comparable for each of the treatment periods. Serum oestradiol levels increased significantly, twofold, 1 h after ingestion of oestradiol but there was no significant change in levels of serum progesterone and testosterone. Lymphocyte beta 2-AR parameters following treatment with oestradiol and progesterone did not change significantly from baseline and were not different from placebo.
In contrast to previously reported effects in women, female sex-steroid hormones did not appear to have any significant facilitatory effects on lymphocyte beta 2-AR parameters when given exogenously to healthy males. This lack of effect may be due either to the absence of receptors for female sex hormones in beta 2-AR or to reduced efficacy of female hormone-receptor coupling in male lymphocytes.
我们之前已经证明,在健康女性的卵泡期给予外源性孕酮而非雌激素时,淋巴细胞β2-肾上腺素能受体(β2-AR)会上调。在本研究中,我们想看看这种女性性激素的促进作用在健康男性中是否也能得到证实。
9名平均年龄为24岁的健康男性志愿者完成了这项随机、双盲、安慰剂对照的交叉研究。他们被随机分配接受口服安慰剂、戊酸雌二醇(4毫克)或甲羟孕酮(40毫克)。研究药物分两次给药,间隔12小时。受试者在基线(T0为基线)、摄入第二剂研究药物后1小时(T1)和24小时后(T24)到实验室就诊。每次就诊时,抽取60毫升外周血用于测量血清雌二醇、孕酮和睾酮水平,以及淋巴细胞β2-AR参数;密度(Bmax)、结合亲和力(Kd)和对异丙肾上腺素的最大环磷酸腺苷反应(Emax)。
每个治疗期的性类固醇激素基线水平相当。摄入雌二醇1小时后,血清雌二醇水平显著升高两倍,但血清孕酮和睾酮水平没有显著变化。用雌二醇和孕酮治疗后,淋巴细胞β2-AR参数与基线相比没有显著变化,且与安慰剂无差异。
与之前报道的对女性的影响相反,外源性给予健康男性女性性激素时,似乎对淋巴细胞β2-AR参数没有任何显著的促进作用。这种缺乏作用可能是由于β2-AR中不存在女性性激素受体,或者是由于男性淋巴细胞中女性激素-受体偶联的效力降低。