Vasopressin and oxytocin in normal reproduction and in the pathophysiology of preterm labour and primary dysmenorrhoea. Development of receptor antagonists for therapeutic use in these conditions.
Vasopressin and oxytocin are synthesised in the hypothalamus and released to the blood stream via the posterior lobe of the hypophysis. Research during later years has shown that these peptides are also produced in other parts of the brain. The secretion to plasma is stimulated by oestrogen, an effect which is counteracted by progestagen. During delivery the fetus can also produce substantial amounts of vasopressin and oxytocin. Additionally, the uterus itself may be a source of these hormones and we have recently found oxytocin mRNA in the endometrium of non-pregnant women with the highest levels around the time of ovulation. In the onset of labour preterm and at term pregnancy vasopressin and oxytocin are centrally involved and in primary dysmenorrhoea the former hormone seems to play a key role in the mechanisms of increased contractions and reduced blood flow in the uterus of the condition. In women with the latter condition the plasma concentration of vasopressin is several-fold higher than that in healthy control persons. Both in pregnant and non-pregnant women the myometrium is activated via specific vasopressin V1a and oxytocin receptors. This vasopressin receptor is different from the vasopressin V1b receptor of the anterior lobe of the hypophysis, which is important in mood changes and V2 receptor of the kidneys mediating fluid reabsorption. At the onset of labour preterm and at term the vasopressin V1a and oxytocin receptors are elevated to a moderate degree. In non-pregnant women the receptor density varies over the menstrual cycle and increase markedly at the onset of menstruation. Substances, which block the uterine vasopressin V1a and oxytocin receptors inhibit preterm labour and primary dysmenorrhoea.
Akerlund
M
M
Department of Obstetrics and Gynaecology, University Hospital of Lund, Sweden. mats.akerlund@gyn.lu.se
D065092:Antidiuretic Hormone Receptor Antagonists; D004412:Dysmenorrhea / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008597:Menstrual Cycle / Q000502:physiology*; D007752:Obstetric Labor, Premature / Q000378:metabolism / Q000503:physiopathology*; D010121:Oxytocin / Q000378:metabolism*; D011247:Pregnancy; D018045:Receptors, Oxytocin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017483:Receptors, Vasopressin / Q000378:metabolism; D014599:Uterus / Q000378:metabolism; D014667:Vasopressins / Q000378:metabolism*
D065092:Antidiuretic Hormone Receptor Antagonists; D018045:Receptors, Oxytocin; D017483:Receptors, Vasopressin; D014667:Vasopressins; D010121:Oxytocin