Effects on Plasma Luteinizing Hormone Levels of Microinjection of Noradrenaline and Adrenaline into the Septo‐Preoptic Area of the Brain of the Ovariectomized Ewe: Changes with Season and Chronic Oestrogen Treatment

Abstract

We have investigated the effects on luteinizing hormone (LH) secretion of noradrenaline (NA) and adrenaline (A) microinjected (1 μl) into the septo-preoptic area of ovariectomized (OVX) ewes with or without oestrogen (E) treatment and across the breeding and non-breeding seasons. Guide tubes (19 gauge) were placed into the septo-preoptic area of OVX ewes using lateral ventriculograms for localization of the target area. The sheep were tamed so that injections could be made into conscious animals during blood sampling procedures. Jugular venous blood was collected at 10-min intervals for 3 h, an injection of NA or A (10 μg) or saline was given and samples collected for a further 3 h. The plasma samples were assayed for LH. On completion of the experiments the brains were sectioned to locate the site of injection. In the non-breeding season of the first year, 9 ewes were used of which 3 had correct guide tube placement; in these 3 ewes NA and A had no effect in OVX ewes. In OVX ewes treated with 0.5 cm Silastic ®implants of E for 1 week, plasma LH levels were reduced from 9.1 ± 1.96 nglrnl before E treatment to 2.8±0.95 ng/ml after E treatment. In these E-treated ewes NA and A caused a robust increase in plasma LH levels. In the breeding season, 9 ewes were used of which 7 had correct guide tube placement; in these 7 ewes NA and A had no effect in OVX ewes. When OVX ewes were treated with 0.5cm E implants, NA or A injection decreased LH interpulse interval. In OVX ewes which received 1.0 cm E, NA caused a pronounced but transient suppression of plasma LH secretion due to an increase in interpulse interval. When 3.0 cm E implants were given to OVX ewes there was a strong suppression of plasma LH secretion with pulsatility abolished; NA injection had no effect in these sheep. In the second year, in the non breeding-season, 17 ewes were used of which 14 had correct guide tube placement although a number of injections were above the target region. NA injection had no effect on plasma LH levels in OVX ewes but had a variable effect on OVX ewes treated with 0.5 cm E implants, depending upon the degree of suppression of plasma LH secretion by E. When plasma LH was fully suppressed by E, injection of 1Opg NA provoked a profound and sustained increase in plasma LH levels. When plasma LH secretion was pulsatile after E treatment, NA injection decreased LH interpulse interval. Similar responses were obtained with 0.5cm E-treated sheep when injected with 1.Opg NA. When OVX ewes were given 3.0cm E implants a small and non-significant (P = 0.09) rise in plasma LH levels occurred, following 10 pg NA injection. These results provide further evidence of involvement of NA/A systems in the regulation of gonadotrophin-releasing hormone (GnRH) secretion at the level of the GnRH cell bodies in the septo-preoptic area, with clear influences of season and E status on this regulation. In the OVX sheep the GnRH pulse generation system is probably subserved by endogenous permissive NA/A input rendering exogenous input ineffective. In the breeding season NAlA can inhibit GnRH/LH secretion in the presence of physiological doses of E whereas in the non-breeding season, E profoundly suppresses GnRH/LH secretion, possibly by the removal of permissive NA inputs, which can be overcome by the injection of NAlA into the septo-preoptic area.