The menstrual cycle of the adult woman depends on the regulatory function of the hypothalamo–pituitary–gonadal axis. Hypothalamic luteinizing hormone releasing hormone (LHRH) plays the central regulatory role in this control. As early as 1932 the German scientists Hohlweg and Junkmann postulated an active sexuality centre, placed over the pituitary gland, as the organ with direct stimulatory effect on the ovaries. It was shown that the stimulatory activity of the pituitary gland depends on hypothalamic function, revealing a neural control mechanism. LHRH is a peptide composed of ten amino acids, first isolated and characterized in 1971. LHRH is secreted by neural cells of the nucleus arcuatus in the mediobasal portion of the hypothalamus. The axons of these neurones are in intimate contact with the vessels of the hypothalamo–pituitary portal system. The pulsatile release of LHRH by the hypothalamic neurones causes the gonadotrophic cells of the pituitary gland, which make up about 10% of the gland's cell mass, to release follicle stimulating hormone (FSH) and luteinizing hormone (LH), also in pulsatile fashion. FSH and LH in turn control follicular maturation and gonadal sex steroid biosynthesis. Circulating LHRH is extremely short-lived, with a plasma half-life of two to five minutes, due to rapid enzymatic degradation by peptidases which preferentially interact with the peptide bonds in position six of the molecule. This short half-life ensures that hypothalamic pulses of LHRH are recognized as single events by pituitary receptors. Conversely, continuous administration of LHRH causes a decrease of LHRH receptor density on the gonadotrophic cells of the pituitary gland, reduced LH and FSH levels, and arrest of follicular maturation and sex steroid biosynthesis. The elucidation of neuroendocrine control of the menstrual cycle in adult women based on these findings is one of the most important observations in reproductive medicine during the last three decades, and has had a major clinical impact on the treatment of hormonal disorders in gynaecology and paediatrics, infertility treatment and oncology.
