Exposure to Endogenous Estrogens During Lifetime

Abstract

The present review summarizes data on the time course and physiological function of the three major endogenous estrogens estrone (E1), 17β-estradiol (E2), and estriol (E3) during the different phases of life in the human female and male. During fetal life, E3 is the most abundant estrogen produced by the fetoplacental unit. E3 affects cerbral development, leads to breast gland swelling in both girls and boys and promotes uterine growth up to a size that is not reached again until puberty. In infancy and childhood estrogen levels are low before the ovaries are stimulated to increase the production of E2 at puberty. In the complex course of maturation, the onset of puberty is characterized by a gradually increasing pulsatile secretion of hypothalamic gonadotropin-releasing hormone followed by a gradual rise of circulating gonadotropin levels. Increasing E2 concentrations in girls promote development of female sex characteristics, menarche, behavioral changes, pubertal growth spurt and finally the closure of epiphysal growth zones. Throughout fertile life of the human female, ovarian E2 remains the major endogenous estrogen. It is produed by the granulos cells of the growing follicle as well as by the corpus luteum. Among other functions, it is important for endometrial proliferation, as a prerequisite for blastocyst implantaion and pregnancy. E2 induces growth of the uterus and maturation of the breast. E2 production declines gradually during late reproductive life; as a consequence, menstrual bleeding ceases with menopause. During postmenopause, the predominant endogenous estrogen is E1, which is mainly produed by adipose tissue from androgenic precursors secreted by the ovarian stroma and the adrenal gland. Decreased estrogen concentrations lead to atrophy of the inner and outer genitalia, osteoprorosis, an increased risk of cardiovascular disease, hot flashes and emotional instability.

In summary, exposure to endogenous estrogens during lifetime in the female varies by several orders of magnitude. The time course of estrogen concentration is characterized by a high-estrogen environment during pregnancy, a decline following birth to the low levels during prepuberty. Onset of sexual maturation is indicated by the rising levels of E2 reaching adult concentrations some years after menarche.