Disinhibition of pituitary LH by intracerebral anti-opioid treatments in sheep

Gary Duane Weesner, Purdue University

Abstract

Experiments were conducted to determine if endogenously produced $\beta$-endorphin (BE) and met-enkephalin (Met-E) exert a physiological inhibition on LHRH release in the central nervous system (CNS) of sheep. Twenty-two mature ewes were implanted with guide tubes through which matched infusion cannulae could subsequently be briefly inserted without discomfort for intracerebral (ic) infusion of three anti-opioid treatments: naloxone (NAL; 50 $\mu$g in 20 $\mu$l), sheep anti-sheep BE (SASBE; 20 $\mu$l of 1:25) or sheep anti-Met-E (AME; 20 $\mu$l of 1:25); and of two control treatments: normal sheep serum (20 $\mu$l of 1:25), or anti-thyroglobulin (20 $\mu$l of 1:25). To detect abrupt disinhibition of LHRH release by anti-opioid treatments, serum LH was quantified at 10 min intervals for 1-2 h before and after each ic infusion. Complete trials consisted of 3-4 different anti-opioid or control ic infusions at a single site over 2-3 days during the luteal phase of recurring estrous cycles. Results were statistically evaluated for each ewe since complete trials were replicated 2-5 times within each ewe and because no two ewes could have ic infusions in exactly identical locations. Anatomical generalizations were possible when LH responses to anti-opioid treatments were similar for several ewes with ic infusion sites in comparable brain regions. However, it was not possible to make such generalizations when infusion sites were not comparable in other ewes. In summary, NAL consistently disinhibited LHRH/LH when infused into the mediobasal hypothalamus (MBH; n = 4), the anterior hypothalamic area (AHA; n = 4), the preoptic area (POA; n = 5), and the basal forebrain (BF; n = 5). SASBE consistently disinhibited LHRH/LH release when infused into the rostral POA/nucleus accumbens region (n = 5) and into the anterolateral hypothalamus (n = 1). SASBE did not alter LH concentrations when infused into the BF (n = 7) or into the hypothalamus (n = 9). AME was ineffective at all SASBE-responsive sites and in the BF (n = 5), but it stimulated LHRH/LH release when infused into the AHA (n = 2) and into the MBH (n = 1). Thus, ic immunoneutralization of endogenous $\beta$-endorphin and of met-enkephalin in selected brain areas relieved the inhibition of LHRH release in luteal phase ewes. It is concluded that these two endogenous opioid peptides are involved in the physiological regulation of LHRH/LH release in the luteal phase ewe, and that they act at different CNS sites.

Degree

Ph.D.

Advisors

Malven, Purdue University.

Subject Area

Neurology

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