The Tissue Specific Role of Estrogen and Progesterone in Human Endometrium and Mammary Gland

Abstract

The purpose of this chapter is to review the tissue-specific role of estrogen (E2) and progesterone (P4) in human endometrium and mammary gland. It is well known that both E2 and P4 are essential for the development and differentiation of human endometrium and mammary gland, but the exact basis for differential tissue-specific signalling of E2 and P4 are still not fully understood. This chapter explores observed functions of two major female steroid hormones and their cognate receptors in normal physiology of human reproductive system but also in assisted reproductive technology and breast cancer treatment. The normal reproductive physiology requires tightly coordinated action of hypothalamus, pituitary gland, ovaries and endometrium. Also functioning of other endocrine units such as the thyroid and adrenal glands are essential for regular ovulation and cyclic changes. The production of ovarian steroid hormones is coordinated by the hypothalamic-pituitarygonadal axis which is activated in puberty (Figure 1). The hypothalamus produces and secretes luteinizing hormone-releasing hormone (LHRH), which binds to its receptors in pituitary gland. This causes cascade of biochemical events culminating in the production of two hormones in pituitary gland, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). LH and FSH are secreted into the general blood circulation and attach to receptors on the ovary, where they trigger ovulation and stimulate the production of E2 and P4. Ovarian steroid hormones themselves have direct role in the development of the inner lining of the uterus but they also act as a positive feedback system to hypothalamus and pituitary gland for continuous cyclic changes until the beginning of menopause (Kanis and Stevenson, 1994). Cholesterol is the building block for all steroid hormones, which is carried into the bloodstream and through a sequence of enzymatic changes is synthesized into final products. In the bloodstream steroid hormones are distributed rapidly throughout the tissues and act on distant targets. This secretory process is called endocrine action and the function of many target tissues as mammary gland, brain, bones, liver and heart are affected by circulating hormones. Steroid hormones can also act very close to their site of secretion