Arisawa M, Snyder G D, De Palatis L, Ho R H, Xu R K, Pan G, McCann S M
Department of Obstetrics/Gynecology, School of Medicine, Keio University, Tokyo, Japan.
Proc Natl Acad Sci U S A. 1989 Sep;86(18):7290-4. doi: 10.1073/pnas.86.18.7290.
To evaluate a possible physiological role of endogenous substance P (SP) in the control of growth hormone (GH; somatotropin) secretion, a specific antiserum against SP (anti-SP) was injected intraventricularly (3 microliters into the third cerebral ventricle) in unanesthetized unrestrained normal male rats. Control rats received an equivalent volume of normal rabbit serum (NRS). Intraventricular injection of the NRS lowered plasma GH concentrations significantly. The lowering was detected on first measurement at 10 min after injection and was maximal at 30 min. This was followed by a return toward the initial levels. Third ventricular injection of antiserum significantly increased plasma GH in comparison with control animals injected with NRS. The effect was observed within 10-20 min, and levels remained elevated for the 120-min duration of the experiment. To confirm the possible inhibitory role of endogenous SP on GH release, 3 microliters of 0.9% NaCl (saline) alone or saline containing a specific antagonist of SP, [D-Pro2,D-Trp7,9]SP, was injected into the third ventricle of normal male rats. The antagonist also increased plasma GH significantly (P less than 0.005) within 5 min compared with values in the saline-injected control group. Levels remained elevated for 30 min but had returned toward control values 60 min after injection. In contrast, synthetic SP significantly decreased plasma GH when injected intravenously or intraventricularly compared with plasma GH in the control saline-injected group. To investigate a possible direct action of SP on GH release from the anterior pituitary gland, we incubated synthetic SP with dispersed anterior pituitary cells for 1 hr. The release of GH from incubated anterior pituitary cells was not affected at any dose of SP (10(-9) to 10(-6) M) tested. These data strongly indicate that endogenous SP has a physiological inhibitory role in the control of GH secretion at the level of the hypothalamus in the male rat.
为评估内源性P物质（SP）在生长激素（GH；促生长素）分泌调控中可能的生理作用，将一种针对SP的特异性抗血清（抗SP）经脑室注射（3微升注入第三脑室）到未麻醉、未束缚的正常雄性大鼠体内。对照大鼠接受等量的正常兔血清（NRS）。脑室注射NRS可显著降低血浆GH浓度。注射后10分钟首次测量时即可检测到降低，30分钟时降至最大。随后又恢复到初始水平。与注射NRS的对照动物相比，第三脑室注射抗血清可显著增加血浆GH。该效应在10 - 20分钟内即可观察到，且在实验的120分钟内水平一直保持升高。为证实内源性SP对GH释放可能的抑制作用，将3微升0.9%氯化钠（生理盐水）或含SP特异性拮抗剂[D - Pro2，D - Trp7，9]SP的生理盐水注入正常雄性大鼠的第三脑室。与注射生理盐水的对照组相比，该拮抗剂在5分钟内也可显著增加血浆GH（P < 0.005）。水平在30分钟内保持升高，但注射后60分钟已恢复到对照值。相反，与注射生理盐水的对照组相比，静脉注射或脑室注射合成SP可显著降低血浆GH。为研究SP对垂体前叶GH释放可能的直接作用，我们将合成SP与分散的垂体前叶细胞孵育1小时。在所测试的任何剂量的SP（10⁻⁹至10⁻⁶ M）下，孵育的垂体前叶细胞释放GH均未受影响。这些数据有力地表明，内源性SP在雄性大鼠下丘脑水平对GH分泌的调控中具有生理抑制作用。
