Is changing hypothalamic activity important for control of ovulation?

Abstract

The activity of the hypothalamic gonadotrophin releasing hormone pulse generator in women with regular ovulatory and anovulatory menstrual cycles was assessed to see whether changes therein are important determinants of normal and impaired ovarian function. Endogenous gonadotrophin releasing hormone secretion was inferred by measurement of the pituitary luteinising hormone response by characterisation of pulsatile luteinising hormone release over eight hours on three occasions during the course of follicular development and once during the luteal stage of the same cycles. In 13 ovulatory cycles (serum progesterone concentration greater than 25 nmol/l) confirmed by ovarian ultrasonography a pronounced variability in luteinising hormone pulse patterns among subjects was compatible with ovulation. In the luteal stage of ovulatory cycles the luteinising hormone interpeak interval (85 min, range 42-125) was significantly longer than that during the early follicular (64 min, 40-103), mid-follicular (62 min, 37-107), and late follicular (59 min, 39-80) stages of the same cycles. Thus in ovulatory cycles no increase in frequency of the gonadotrophin releasing hormone pulse generator was detected during follicular development, though this activity decreased in the luteal stage. In five late follicular stage studies in which part of the preovulatory luteinising hormone surge was captured no change in pulse frequency of luteinising hormone was detected compared with the mid-follicular stage of the same cycles or when compared with the late follicular stage of other cycles when no luteinising hormone surge was captured. Though mean luteinising hormone concentrations in luteinising hormone surge series (36 IU/l) were high, the amplitude of luteinising hormone pulses (165%) was only slightly greater than during non-surge late follicular stage studies (145%). Hence no change in hypothalamic gonadotrophin releasing hormone activity is required to generate the preovulatory discharge of luteinising hormone in man, which occurs as a result of the sensitising action of rising oestradiol concentrations on pituitary responsiveness to the same hypothalamic input signal. Luteinising hormone pulse frequency, peak amplitude, and mean serum luteinising hormone concentrations in seven anovulatory cycles (progesterone concentration less than 10 nmol/l) were not different from those at comparable stages of ovulatory cycles. These data suggest that the primary abnormality in this group of regularly menstruating anovulatory women lies in the ovary rather than in the hypothalamic control of the anterior pituitary.