Jansson J O, Ekberg S, Isaksson O, Mode A, Gustafsson J A
Endocrinology. 1985 Nov;117(5):1881-9. doi: 10.1210/endo-117-5-1881.
The influence of endogenous sex steroids and exogenous testosterone treatment on pulsatile GH secretion, body weight, longitudinal bone growth, and hepatic steroid metabolism was studied in male and female adult rats. Blood samples were obtained from the tip of the tail, and maximum and minimum GH levels were determined in individual rats to evaluate pulse heights and baseline levels. Longitudinal bone growth was measured using the intravital marker tetracycline, and hepatic steroid metabolism was evaluated by determining the enzyme activities of 16 alpha-hydroxylase and 5 alpha-reductase. Neonatal, but not prepubertal, gonadectomy of male rats suppressed maximum and mean plasma GH levels during adult life. The body weight and the rate of longitudinal bone growth were also decreased. Testosterone treatment neonatally reversed all of these effects. Neonatal gonadectomy of male rats also caused an elevation of minimum plasma GH levels, an effect, however, which was not reversed by testosterone replacement during neonatal life. Neonatally gonadectomized females treated with testosterone neonatally or during adult life increased their maximum and decreased their minimum GH levels. Their longitudinal bone growth was increased. The body weight of these rats was increased by neonatal, but not adult, testosterone treatment. There was no effect of neonatal ovariectomy on plasma GH levels in 3- to 4-month-old female rats. However, neonatal ovariectomy did increase the maximum and mean plasma GH levels immediately postpubertally, suggesting that the effect of the ovaries on GH secretion differs among mature female rats of different ages. Prepubertal gonadectomy of male rats feminized their hepatic steroid metabolism by decreasing 16 alpha-hydroxylase and increasing 5 alpha-reductase activities. Neonatal gonadectomy caused an even more pronounced feminization, which was partly reversed in rats given testosterone replacement therapy neonatally. In neonatally gonadectomized female rats, treatment with testosterone during adult life increased 16 alpha-hydroxylase and decreased 5 alpha-reductase to levels seen in intact male rats. The present results indicate that neonatally secreted testicular androgens imprint the high amplitude pulses characteristic of GH secretion in adult male rats. Neonatal androgens also stimulate somatic growth and partially account for the masculinized hepatic steroid metabolism in the adult animal. It is proposed that imprinting of the GH secretory pattern contributes to the influence of neonatal testicular androgens on body growth and hepatic steroid-metabolizing enzymes.
研究了内源性性类固醇和外源性睾酮治疗对成年雄性和雌性大鼠脉冲式生长激素（GH）分泌、体重、纵向骨生长以及肝脏类固醇代谢的影响。从大鼠尾尖采集血样，测定每只大鼠的GH最高水平和最低水平，以评估脉冲高度和基线水平。使用活体标记物四环素测量纵向骨生长，并通过测定16α-羟化酶和5α-还原酶的酶活性来评估肝脏类固醇代谢。雄性大鼠新生期而非青春期前进行性腺切除，会抑制成年期血浆GH的最高水平和平均水平。体重和纵向骨生长速率也会降低。新生期给予睾酮治疗可逆转所有这些影响。雄性大鼠新生期性腺切除还会导致血浆GH最低水平升高，不过，新生期给予睾酮替代治疗并不能逆转这一效应。新生期接受性腺切除的雌性大鼠，在新生期或成年期给予睾酮治疗后，其GH最高水平升高，最低水平降低。它们的纵向骨生长增加。新生期而非成年期给予睾酮治疗可增加这些大鼠的体重。新生期卵巢切除对3至4月龄雌性大鼠的血浆GH水平没有影响。然而，新生期卵巢切除确实会在青春期后立即增加血浆GH的最高水平和平均水平，这表明卵巢对GH分泌的影响在不同年龄的成年雌性大鼠中有所不同。雄性大鼠青春期前进行性腺切除，会通过降低16α-羟化酶活性和增加5α-还原酶活性使肝脏类固醇代谢女性化。新生期性腺切除导致更明显的女性化，在新生期给予睾酮替代治疗的大鼠中这种情况部分得到逆转。在新生期接受性腺切除的雌性大鼠中，成年期给予睾酮治疗可使16α-羟化酶活性增加，5α-还原酶活性降低至完整雄性大鼠的水平。目前的结果表明，新生期分泌的睾丸雄激素为成年雄性大鼠GH分泌的高幅度脉冲特征打下印记。新生期雄激素还刺激体细胞生长，并部分解释了成年动物肝脏类固醇代谢的男性化现象。有人提出，GH分泌模式的印记有助于新生期睾丸雄激素对身体生长和肝脏类固醇代谢酶的影响。
