Neuropeptide regulation of hormone secretion

The actions of LHRH, CRH and NPY on the activity of the reproductive axis and, in particular, the LHRH pulse generator were investigated in vivo. A model was developed to allow direct administration of neuro¬ peptides, antagonists and antibodies into the third cerebral ventricle of conscious, free-moving and unstressed sheep, giving access to hypo¬ thalamic periventricular structures involved in the control of the anterior pituitary gland. Plasma levels of LH were used as a measure of LHRH pulsatility. Three major questions were addressed: 1 (1) Does hypothalamic LHRH autoregulate its own release? Injection of LHRH (2.1-21 pmol) into the third ventricle caused a specific, doserelated and receptor-mediated inhibition of LH secretion. It is therefore suggested that the intrinsic communication between LHRH neurones may be inhibitory and may provide a mechanism to affect the timing of the pulsatile release of LHRH. However, as central injection of LHRH also caused a rapid 4-5-fold rise in plasma Cortisol levels, prior to and correlated with the reduction in LH secretion, this inhibitory commun¬ ication may be indirect. (2) Does CRH act as a central neurotransmitter to mediate the inhibitory effects of stress on LHRH release? In contrast to other species, central injection of CRH (0.12-1.2 nmol) caused a dose-related stimulation of LH secretion, due to a significant increase in LH pulse frequency. CRH also caused a marked and dose-related stimulation of prolactin and Cortisol secretion, two hormones known to be released under conditions of stress. Endogenous opioid peptides were shown to mediate the central effect of CRH on the release of prolactin, but not on LH or Cortisol. The effect on LH may reflect a species difference, or alternatively may be similar to the increase in LH secretion reported in rats and monkeys subjected to short-term handling or restraint stress. These data provide evidence that CRH acts as a central neurotransmitter; i.e., distinct from its action as a secretagogue for ACTH. (3) Does central NPY interact with LHRH and/or CRH to modulate the reproductive axis? In contrast to the rat, central injection of NPY (0.151.5 nmol) had no effect on LH levels in ovariectomized ewes with or