title: Effects of N-methyl-D,L-aspartic acid on luteinizing hormone secretion in normal mice and in hypogonadal mice with fetal preoptic area implants.
abstract: Many aspects of reproductive function are corrected in hypogonadal mice with preoptic area grafts (HPG/POA). Gonadotropin release and gonadal development are dependent on the presence of GnRH cells within the grafts and GnRH innervation of the median eminence. This study examined the effect of a known modulator of GnRH secretion, N-methyl-D,L-aspartic acid (NMA), in adult normal and HPG/POA male and female mice. All HPG/POA males had significant testicular development after graft surgery, and most HPG/POA females were in constant vaginal estrus and showed ovarian and uterine development; a few also demonstrated ovulatory cyclicity after pregnancies initiated by reflex ovulation. Groups of normal and HPG/POA males that were intact (INT) or castrated (CX) 7 days before testing were challenged with saline, NMA (20 mg/kg), and GnRH (100 ng/0.1 ml). Sequential blood samples from awake animals were obtained via intracardiac catheters for evaluation of plasma LH. There were significant increases in plasma LH after NMA challenge in normal INT [n = 15; 0 min, 0.26 +/- 0.02 (mean +/- SE); 10 min, 1.20 +/- 0.10 ng/ml; P less than 0.05] and normal CX (n = 13; 0 min, 0.36 +/- 0.06, 10 min, 3.25 +/- 0.27). Plasma LH secretion in response to NMA was significantly correlated (r = 0.786; P less than 0.001) with plasma LH release after the GnRH challenge in normal males. In contrast, only 3 of 17 HPG/POA (1 INT and 2 CX) showed increased circulating LH after NMA challenge, despite heightened pituitary sensitivity to GnRH. Normal and HPG/POA female mice were ovariectomized (OX) or OX and estrogen primed (OXE2) 7 days before testing. Intact cycling normal and cycling HPG/POA mice were tested in estrus (EST). There was a greater response to NMA in normal OX (n = 8; 0 min, 0.39 +/- 0.02; 10 min, 1.44 +/- 0.28) than in OXE2 (n = 13; 0 min, 0.29 +/- 0.01; 10 min, 0.52 +/- 0.07) despite similar gonadotroph sensitivity to GnRH. There was also a significant increase in plasma LH in response to NMA in HPG/POA-OX (n = 7; 0 min, 0.50 +/- 0.10; 10 min, 1.62 +/- 0.22) and HPG/POA-OXE2 (n = 12; 0 min, 0.39 +/- 0.04; 10 min, 1.31 +/- 0.26). Plasma LH levels after NMA treatment were significantly correlated with responses to GnRH in female HPG/POA (r = 0.58; P less than 0.03), but not in normal females. Neither normal-EST nor HPG/POA-EST had increased LH release after NMA challenge, perhaps due to the low gonadotroph sensitivity in this state.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029.
authors.forename: Y
authors.initials: Y
authors.lastname: Saitoh
authors.forename: A J
authors.initials: AJ
authors.lastname: Silverman
authors.forename: M J
authors.initials: MJ
authors.lastname: Gibson
mesh_terms: D000818:Animals; D002369:Castration; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D016332:Fetal Tissue Transplantation; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D006066:Gonads / Q000473:pathology; D007006:Hypogonadism / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D016202:N-Methylaspartate / Q000494:pharmacology*; D009929:Organ Size; D011301:Preoptic Area / Q000196:embryology*; D012016:Reference Values
chemical_list: D004967:Estrogens; D007987:Gonadotropin-Releasing Hormone; D016202:N-Methylaspartate; D007986:Luteinizing Hormone