The central oxytocin pulse generator: a pacemaker for the ovarian cycle

During luteolysis in sheep, episodic pulses of oxytocin (OT), contributed by the neurohypophysis and the corpus luteum (CL), stimulate uterine luteolytic pulses of prostaglandin (PG) F2 alpha via endometrial OT receptors. To distinguish relative contributions of neurohypophysial and luteal OT, ovariectomized sheep were given estradiol-17 beta (E) and progesterone (P) to stimulate levels during the cycle. In intact sheep, luteectomy was performed to exclude the CL as a source of OT and to initiate P withdrawal. In ovariectomized sheep, E (1 microgram/h) for 12 to 36 h) superimposed on basal E(0.05 microgram/h), caused a series of 4 to 6 episodes of high frequency pulses of OT, each episode lasting 1 to 2 h at intervals of 3 h, and commencing at 24 h. Withdrawal of P (500 micrograms/h), superimposed on basal E in ovariectomized sheep, or luteectomy in intact sheep, evoked similar episodes of high frequency pulses of OT beginning at 24 h. We conclude that (1) an increase in E levels, or the return of E action following P withdrawal, causes intermittent increases in the frequency of the central OT pulse generator. (2) high frequency pulses of OT initiate subluteolytic levels of uterine PGF2 alpha which trigger a supplemental release of luteal OT; (3) luteal OT amplifies the secretion of uterine PGF2 alpha which initiates luteolysis and causes more luteal OT to be secreted; and (4) in addition to the established hypothalamic-anterior pituitary-gonadal axis for initiating the ovarian cycle (via the gonadotrophins), there is now evidence for a hypothalamic-posterior pituitary-gonadal axis for terminating the ovarian cycle (via OT).