Endocrine Abstracts

The molecular and cellular mechanisms within the uterine endometrium regulating menstruation, involve complex interactions between the endocrine, vascular and immune systems. The endometrium is a dynamic tissue that undergoes characteristic changes (proliferation, differentiation and shedding) each menstrual cycle as a consequence of sequential exposure to the ovarian sex steroids. Oestrogen and progesterone, via their cognate receptors regulate the expression of a cascade of local factors within the endometrium that act in an autocrine, paracrine and intracrine manner. Members of the nuclear receptor super-family expressed by endometrial cells include progesterone (PR), oestrogen (ERα,ß), androgen (AR) and glucocorticoid receptors (GR). The withdrawal of progesterone is the trigger for menstruation.

Following shedding of the upper functional layer, the endometrium displays remarkable and immediate regenerative capacity. The precise local mechanisms involved in control of this highly coordinated cyclical tissue ‘injury’ and ‘repair’ have yet to be fully elucidated.

Endometrial local cellular concentrations of steroids are regulated by hydroxysteroid dehydrogenase enzymes. These enzymes determining ligand availability are in turn regulated at the local cellular level by endocrine signals and may be further modulated by exogenous steroid administration.

Valuable insight about progesterone action and endometrial function has come from the observations of pharmacological withdrawal of progesterone from the endometrium. Studies with PR modulators (PRMs) have identified local mechanisms that may be targeted in order to modulate endometrial bleeding.

In developed countries today women expect to menstruate over 400 times during their reproductive life span and disorders of menstruation have a major impact on the quality of life of many women. Determination of the endocrine regulation of endometrial function and the molecular and cellular pathways responsible for both normal and aberrant menstruation will provide much needed insight into causes of menstrual dysfunction. Future research efforts should aim to delineate pathways that may be targets for therapeutic intervention.