Kletter G B, Padmanabhan V, Beitins I Z, Marshall J C, Kelch R P, Foster C M
Department of Pediatrics, University of Michigan, Ann Arbor 48105, USA.
J Clin Endocrinol Metab. 1997 Dec;82(12):4010-4. doi: 10.1210/jcem.82.12.4458.
We have shown previously in pubertal boys that testosterone (T) suppresses the nocturnal augmentation of luteinizing hormone (LH) secretion principally by decreasing LH pulse frequency. As T can be aromatised to estradiol (E2), and E2 effects on LH secretory dynamics may be separate from those of T, we examined the effects of acute E2 infusion on LH secretion in pubertal boys. Opioid receptor blockade has been reported to increase LH secretion after estradiol suppression in adult men, so we also examined whether naloxone might augment LH secretion during E2 treatment in pubertal boys. Starting at 1000 h, eight pubertal boys were given a 33 h saline infusion, followed 1 week later by an E2 infusion at 4.6 nmol/m2/h. During both infusions, four iv boluses of saline were given hourly beginning at 1200 h on the first day, and four naloxone iv boluses, 0.1 mg/kg each, were given hourly beginning at 1200 h on the second day. Blood was obtained every 15 min for LH, and every 60 min for T and E2, from 1200 h until the end of the infusion. Pituitary responsiveness to gonadotropin-releasing hormone (GnRH) was assessed after both infusions by iv administration of 250 ng/kg synthetic GnRH. Estradiol infusion increased the mean plasma E2 concentration from 23 +/- 4 to 46 +/- 6 pmol/L (P < 0.01) and suppressed mean plasma T from 4.9 +/- 1.4 to 3.0 +/- 3.5 nmol/L (saline vs. E2 infusion, P < 0.05). The overall mean LH was suppressed by E2 infusion from 3.7 +/- 0.5 to 2.2 +/- 0.4 IU/L (saline vs. E2 infusion, P < 0.01). LH pulse frequency was suppressed by 50%, whereas mean LH pulse amplitude was not different between saline and E2 infusions. Administration of naloxone did not alter the mean LH, LH pulse frequency, or amplitude during either saline or E2 infusions. Pituitary responsiveness to exogenous GnRH was similar during both infusions. These studies indicate that E2 produces its negative feedback in pubertal boys principally by suppression of LH pulse frequency, and naloxone does not reverse these suppressive effects. Thus E2 suppression of LH secretion is mediated by a decrease of hypothalamic GnRH secretion that is independent of endogenous opioid pathways.
我们之前已在青春期男孩中证实，睾酮（T）主要通过降低促黄体生成素（LH）脉冲频率来抑制LH夜间分泌增加。由于T可芳香化转化为雌二醇（E2），且E2对LH分泌动力学的影响可能与T不同，我们研究了急性输注E2对青春期男孩LH分泌的影响。据报道，在成年男性中，阿片受体阻断可在雌二醇抑制后增加LH分泌，因此我们还研究了纳洛酮是否会在青春期男孩E2治疗期间增加LH分泌。从上午10点开始，对8名青春期男孩进行33小时的生理盐水输注，1周后以4.6 nmol/m²/h的速度输注E2。在两次输注期间，从第一天中午12点开始每小时静脉注射4次生理盐水推注，从第二天中午12点开始每小时静脉注射4次纳洛酮推注，每次0.1 mg/kg。从中午12点到输注结束，每15分钟采集一次血液用于检测LH，每60分钟采集一次血液用于检测T和E2。在两次输注后，通过静脉注射250 ng/kg的合成促性腺激素释放激素（GnRH）来评估垂体对GnRH的反应性。输注E2使平均血浆E2浓度从23±4 pmol/L升高至46±6 pmol/L（P<0.01），并使平均血浆T从4.9±1.4 nmol/L降至3.0±3.5 nmol/L（生理盐水输注与E2输注相比，P<0.
