Vermeulen A
Department of Endocrinology and Metabolism, State University of Ghent, Belgium.
Environ Health Perspect. 1993 Jul;101 Suppl 2(Suppl 2):91-100. doi: 10.1289/ehp.93101s291.
As the hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator is an integrator of hormonal, metabolic, and neural signals, it is not surprising that the function of the hypothalamogonadal axis is subject to the influence of a large array of environmental factors. Before puberty, the central nervous system (CNS) restrains the GnRH pulse generator. Undernutrition, low socioeconomic status, stress, and emotional deprivation, all delay puberty. During reproductive life, among peripheral factors that effect the reproductive system, stress plays an important role. Stress, via the release of corticotropin-releasing factor (CRF), eventually triggered by interleukin 1, inhibits GnRH release, resulting in hypogonadism. Effects of CRF are probably mediated by the opioid system. Food restriction and underweight (anorexia nervosa), obesity, smoking, and alcohol all have negative effects on the GnRH pulse generator and gonadal function. Age and diet are important determinants of fertility in both men and women. The age-associated decrease in fertility in women has as a major determinant chromosomal abnormalities of the oocyte, with uterine factors playing a subsidiary role. Age at menopause, determined by ovarian oocyte depletion, is influenced by occupation, age at menarche, parity, age at last pregnancy, altitude, smoking, and use of oral contraceptives. Smoking, however, appears to be the major determinant. Premature menopause is most frequently attributable to mosaicism for Turner Syndrome, mumps ovaritis, and, above all, total hysterectomy, which has a prevalence of about 12-15% in women 50 years old. Premature ovarian failure with presence of immature follicles is most frequently caused by autoimmune diseases or is the consequence of irradiation or chemotherapy with alkylating cytostatics. Plasma estrogens have a physiological role in the prevention of osteoporosis. Obese women have osteoporosis less frequently than women who are not overweight. Early menopause, suppression of adrenal function (corticoids), and thyroid hormone treatment all increase the frequency of osteoporosis. Aging in men is accompanied by decreased Leydig cell and Sertoli cell function, which has a predominantly primary testicular origin, although changes also occur at the hypothalamopituitary level. Plasma testosterone levels, sperm production, and sperm quality decrease, but fertility, although declining, is preserved until senescence. Stress and disease states accelerate the decline on Leydig cell function. Many occupational noxious agents have a negative effect on fertility.(ABSTRACT TRUNCATED AT 400 WORDS)
由于下丘脑促性腺激素释放激素(GnRH)脉冲发生器是激素、代谢和神经信号的整合器,下丘脑-性腺轴的功能受到大量环境因素的影响也就不足为奇了。青春期前,中枢神经系统(CNS)抑制GnRH脉冲发生器。营养不良、社会经济地位低下、压力和情感剥夺都会延迟青春期。在生殖期,在影响生殖系统的外周因素中,压力起着重要作用。压力通过促肾上腺皮质激素释放因子(CRF)的释放,最终由白细胞介素1触发,抑制GnRH释放,导致性腺功能减退。CRF的作用可能由阿片系统介导。食物限制和体重过轻(神经性厌食症)、肥胖、吸烟和饮酒都会对GnRH脉冲发生器和性腺功能产生负面影响。年龄和饮食是男性和女性生育能力的重要决定因素。女性生育能力随年龄的下降主要由卵母细胞染色体异常决定,子宫因素起次要作用。绝经年龄由卵巢卵母细胞耗竭决定,受职业、初潮年龄、产次、末次妊娠年龄、海拔、吸烟和口服避孕药使用情况的影响。然而,吸烟似乎是主要决定因素。过早绝经最常见的原因是特纳综合征的嵌合体、流行性腮腺炎卵巢炎,最重要的是全子宫切除术,在50岁女性中的患病率约为12-15%。存在未成熟卵泡的卵巢早衰最常见的原因是自身免疫性疾病,或是放射或使用烷化细胞抑制剂化疗的结果。血浆雌激素在预防骨质疏松症中具有生理作用。肥胖女性患骨质疏松症的频率低于非超重女性。过早绝经、肾上腺功能抑制(皮质类固醇)和甲状腺激素治疗都会增加骨质疏松症的发生率。男性衰老伴随着睾丸间质细胞和支持细胞功能的下降,这主要源于原发性睾丸,尽管下丘脑-垂体水平也会发生变化。血浆睾酮水平、精子生成和精子质量下降,但生育能力虽然下降,但直到衰老仍能维持。压力和疾病状态会加速睾丸间质细胞功能的下降。许多职业有害因素会对生育能力产生负面影响。(摘要截选至400字)