Endocrine Abstracts

While secretion of GnRH pulses from hypothalamic neurones every 1 to 4 h is the normal mode of release in adult males and females, resulting in pulsatile LH secretion from pituitary gonadotropes, only in females does the pattern of GnRH secretion change from pulsatile to a surge mode in response to estradiol to generate the preovulatory LH surge. We have investigated the changes in gonadotropes which ensure that they are responsive to the GnRH surge allowing the release of sufficient LH for ovulation. An increase in the number of gonadotropes expressing ERa during the follicular phase of the cycle occurs that coincides with increased GnRH receptor expression dependent on estradiol. Just before preovulatory LH surge onset there is a major polarisation of LH-containing granules within gonadotropes to the membrane abutting capillaries. This occurs as a co-ordinated response to the increase in both estradiol and GnRH pulsatile secretion during the follicular phase of the cycle. During the preovulatory LH surge over 80% of the pituitary content of LH is released associated with release of all LH granules. Gonadotropes become devoid of granules and pulsatile LH secretion does not return until granules of LH reappear. All these profound changes in LH occur with little change in levels of LHβ mRNA and a reduction in transcription rate, although there are changes in polyadenylation of the LH mRNA. Thus packaging of LH into storage granules, and the intracellular movement and subsequent release of granules in response to GnRH plays a crucial role in the generation of the preovulatory LH surge. Current research is focussing on the intracellular mechanisms regulating the packaging of LH and FSH within gonadotropes indicating that the LHβ subunit itself may play a crucial role in organising the packaging of LH into granules.

Thanks to Janet Crawford, Linda Nicol and Judy McNeilly