It has recently become patently clear that the concept of """"""""blood concentration"""""""" of a given pituitary hormone may be relatively meaningless in light of the discovery that these hormones are secreted in a rhythmic, pulsatile manner. The pattern of hormone release seems to be far more important that the quantity in determining the response of the target tissue(s). Yet despite the recognized importance of pulsatile hormone secretion, very little is known about the effects of altering the parameters (frequency, duration, shape, amplitude, etc.) of the pulsatile signal on the target response. The proposed projects examine several important aspects of pulsatile pituitary hormone secretion and will lay the groundwork for changes in the way endocrine problems are evaluated and treated. First, the pulsatile pattern of LH and FSH secretion will be characterized in freely moving, cannulated rats. An emphasis will be placed on elucidating separate control mechanisms for the pulsatile release of the two gonadotropins. Secondly, the effects of altering the parameters of pulsatile input signals on LH-FSH and ACTH-Beta-endorphin release from incubating pituitaries will be determined using a computer-controlled perifusion apparatus. Since we are one of the few, if not the only, laboratory in the world with this capability, our contribution to the knowledge of pulsatile hormone regulation will be quite unique. In addition, the possibility of spontaneous pituitary pulses (without external stimulation) will be examined. Thirdly, the effect of altering hormonal input signals on the intracellular messengers regulating cellular responses will be studied using the computer assisted perifusion system and monolayer pituitary cultures. In particular, the phenomena of desensitization and sensitization will be examined to elucidate the responsible intracellular messenger system(s). Information gained from these studies should be almost immediately translatable into information for improving treatments of infertility and for future prospects of fertility regulation.
