CORTICOTROPIN-RELEASING HORMONE MEDIATES SUPPRESSION OF PULSATILE LUTEINIZING-HORMONE SECRETION INDUCED BY ACTIVATION OF ALPHA-ADRENERGIC RECEPTORS IN THE PARAVENTRICULAR NUCLEUS IN FEMALE RATS

The present study examined which subtype of adrenergic receptor in the paraventricular nucleus (PVN) has a role in regulating pulsatile LH secretion and whether CRH mediates the effect of norepinephrine (NE) injection into the PVN on pulsatile LH secretion in ovariectomized (OVX) and ovariectomized estradiol (E(2))-treated (OVX+E(2)) rats. All animals were OVX, and some were sc implanted with Silastic capsules containing E(2) dissolved in peanut oil. One week after ovariectomy and E(2) implantation, guide cannulae for injection of agent and alpha-helical CRF-(9-41) (alpha-hel CRF), anantagonist of CRH, were stereotaxically implanted into the PVN and third ventricle, respectively. Animals were bled for 3 h at 6-min intervals through an atrial cannula immediately after PVN injection of NE or various adrenergic receptor agonists (phenylephrine, an alpha(1)-adrenergic receptor agonist; clonidine, an alpha(2)-agonist; and isoproterenol, a beta-agonist). Some of the animals were injected with alpha-hel CRF 5 min before NE injection. NE and both alpha-receptor agonists inhibited pulsatile LH secretion throughout the 3-h sampling period in OVX+E(2) rats and significantly reduced the mean plasma LH levels and the LH pulse frequency. On the other hand, LH secretion was inhibited transiently for the first 1-2 h by an injection of NE or an alpha(2)-receptor agonist into the PVN in OVX rats, resulting in a significant decrease only in mean plasma LH levels in the NE-injected group. Injection of a beta-agonist did not affect pulsatile LH secretion in either OVX or OVX+E(2) animals. Intracerebroventricular injection of alpha-hel CRF before PVN injection of NE completely blocked the NE-induced suppression of pulsatile LH secretion in OVX+E(2) rats. These results suggest that 1) the noradrenergic system projecting to the PVN suppresses pulsatile LH secretion via the activation of alpha-adrenergic receptors; 2) this inhibition is mediated by CRH release; and 3) estrogen enhances this suppression.