PMID- 2184021 OWN - NLM STAT- MEDLINE DCOM- 19900525 LR - 20181130 IS - 0013-7227 (Print) IS - 0013-7227 (Linking) VI - 126 IP - 5 DP - 1990 May TI - Metabolic interfaces between growth and reproduction. III. Central mechanisms controlling pulsatile luteinizing hormone secretion in the nutritionally growth-limited female lamb. PG - 2719-27 AB - Growth retardation induced by dietary restriction in the lamb results in a low frequency of episodic LH secretion and, thus, delayed puberty. Such lambs respond normally to physiological doses of GnRH, indicating that the pituitary gland can function adequately during diet-induced hypogonadotropism. The current studies investigated central mechanisms underlying diet-induced hypogonadotropism. The first aim was to determine whether the hypothalamic GnRH secretory system is capable of normal function. The initial approach was to compare hypothalamic GnRH content between lambs on a restricted diet with low LH pulse frequency (less than 1 pulse/4 h; n = 5) and lambs on an ad libitum diet with high LH pulse frequency (4.5 +/- 0.4 pulses/4 h; n = 5). RIA of extracts of preoptic area and mediobasal hypothalamus/median eminence tissue blocks revealed no differences in GnRH content between lambs on a restricted diet and those on an ad libitum diet. The second approach was to determine if LH secretion could be induced by chemical stimulation of neuronal function with N-methyl-D,L-aspartate (NMA), an excitatory amino acid agonist. Initially, a single iv bolus of NMA was given to hypogonadotropic lambs on a restricted diet. There was a dose-dependent immediate rise in serum LH concentrations. All lambs responded to the highest dose (5.0 mg/kg BW; n = 6), and four of five lambs responded to the intermediate dose (1.0 mg/kg). No lambs responded to the lowest dose (0.2 ng/kg), despite a normal response to GnRH (2.5 ng/kg BW, iv). In a second experiment, hypogonadotropic lambs on a restricted diet were treated with repeated injections of NMA (5 mg/kg BW, iv) at either hourly intervals (n = 6) or every 3 h (n = 6). Each NMA injection induced a LH pulse in both treatment regimens over the entire 7-h experimental period. Thus, the nutritionally growth-limited lamb is capable of sustained production of LH pulses, which, we presume, reflect GnRH secretion. The second aim was to test the hypothesis that endogenous opioid mechanisms inhibit LH secretion during nutritionally induced hypogonadotropism, because opioid pathways are a poor inhibitory regulator of LH secretion in the normally developing sheep, even in the absence of ovarian steroids. We were unable to detect any effects of the opiate antagonist naloxone on LH secretion in the nutritionally growth-limited lamb. We conclude that central mechanisms controlling the release, rather than synthesis, of GnRH are limiting LH secretion when sexual maturation is delayed by growth retardation. Moreover, opioid inhibition is not the primary reason for hypogonadotropism during dietary restriction. FAU - Ebling, F J AU - Ebling FJ AD - Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor 48109-0404. FAU - Wood, R I AU - Wood RI FAU - Karsch, F J AU - Karsch FJ FAU - Vannerson, L A AU - Vannerson LA FAU - Suttie, J M AU - Suttie JM FAU - Bucholtz, D C AU - Bucholtz DC FAU - Schall, R E AU - Schall RE FAU - Foster, D L AU - Foster DL LA - eng GR - HD-07048/HD/NICHD NIH HHS/United States GR - HD-18258/HD/NICHD NIH HHS/United States GR - HD-18394/HD/NICHD NIH HHS/United States GR - etc. PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Endocrinology JT - Endocrinology JID - 0375040 RN - 30KYC7MIAI (Aspartic Acid) RN - 33515-09-2 (Gonadotropin-Releasing Hormone) RN - 36B82AMQ7N (Naloxone) RN - 6384-92-5 (N-Methylaspartate) RN - 9002-67-9 (Luteinizing Hormone) SB - IM MH - Animals MH - Aspartic Acid/administration & dosage/analogs & derivatives/pharmacology MH - Dose-Response Relationship, Drug MH - Female MH - *Food Deprivation MH - Gonadotropin-Releasing Hormone/metabolism MH - Growth Disorders/etiology/*physiopathology MH - Hypothalamus, Middle/metabolism MH - Luteinizing Hormone/*metabolism MH - Median Eminence/metabolism MH - N-Methylaspartate MH - Naloxone/pharmacology MH - Preoptic Area/metabolism MH - Sheep EDAT- 1990/05/01 00:00 MHDA- 1990/05/01 00:01 CRDT- 1990/05/01 00:00 PHST- 1990/05/01 00:00 [pubmed] PHST- 1990/05/01 00:01 [medline] PHST- 1990/05/01 00:00 [entrez] AID - 10.1210/endo-126-5-2719 [doi] PST - ppublish SO - Endocrinology. 1990 May;126(5):2719-27. doi: 10.1210/endo-126-5-2719.