Ogura K, Irahara M, Kiyokawa M, Tezuka M, Matsuzaki T, Yasui T, Kamada M, Aono T
Department of Obstetrics and Gynecology, University of Tokushima School of Medicine, 3-18-15, Kuramoto-cho, Tokushima City, Tokushima 770-8503, Japan.
Eur J Endocrinol. 2001 Jun;144(6):653-8. doi: 10.1530/eje.0.1440653.
Leptin, which is the product of the obese gene, is believed to play important roles in pubertal development and reproductive function in females. In a study using adult male rats, it was found that leptin stimulated secretion of gonadotropin from the pituitary in a dose-related manner. However, there has been no such study in female rats.
To investigate the effects of leptin on the production of LH and FSH from the pituitary in female rats, using primary cultured pituitary cells.
In this study, we determined body weight, serum leptin concentration and serum estradiol (E(2)) concentration in female Wistar rats at 3, 5, 6, 7, 9 and 11 weeks of age, and cultured pituitary cells from 6-week-old female Wistar rats with leptin (0--10(-7) mol/l) and GnRH (0 or 10(-8) mol/l). Then basal and GnRH-stimulated extra- and intracellular LH and FSH were assayed by RIA.
Serum leptin concentration increased with increases in body weight and E(2) concentration. The pubertal serum leptin concentration was about 10(-10) mol/l. At a lower or moderate concentration, leptin produced dose-related increases in both basal and GnRH-stimulated extra- and intracellular LH and FSH in pituitary cells. At a concentration of 10 mol/l, leptin significantly (P<0.05) stimulated both basal and GnRH-stimulated extra- and intracellular LH and FSH. However, at greater concentrations, these effects diminished.
These results indicated that leptin induced pituitary cells to produce and secrete both LH and FSH, with or without GnRH. The concentration of leptin that induced the greatest production of gonadotropins by pituitary cells was 10(-10) mol/l, which was the same as the physiological pubertal concentration. Leptin may be involved in the onset of puberty. It is also conceivable that leptin may be a cause of ovulatory failure, not only in weight loss but also in weight gain.
瘦素是肥胖基因的产物,被认为在雌性动物的青春期发育和生殖功能中发挥重要作用。在一项使用成年雄性大鼠的研究中,发现瘦素以剂量相关的方式刺激垂体促性腺激素的分泌。然而,在雌性大鼠中尚未有此类研究。
使用原代培养的垂体细胞,研究瘦素对雌性大鼠垂体促黄体生成素(LH)和促卵泡生成素(FSH)分泌的影响。
在本研究中,我们测定了3、5、6、7、9和11周龄雌性Wistar大鼠的体重、血清瘦素浓度和血清雌二醇(E₂)浓度,并将6周龄雌性Wistar大鼠的垂体细胞与瘦素(0 - 10⁻⁷ mol/L)和促性腺激素释放激素(GnRH,0或10⁻⁸ mol/L)一起培养。然后通过放射免疫分析法测定基础状态下以及GnRH刺激后的细胞外和细胞内LH和FSH水平。
血清瘦素浓度随体重和E₂浓度的增加而升高。青春期血清瘦素浓度约为10⁻¹⁰ mol/L。在较低或中等浓度下,瘦素使垂体细胞基础状态下以及GnRH刺激后的细胞外和细胞内LH和FSH呈剂量相关增加。在10⁻¹⁰ mol/L浓度时,瘦素显著(P<0.05)刺激基础状态下以及GnRH刺激后的细胞外和细胞内LH和FSH。然而,在更高浓度时,这些作用减弱。
这些结果表明,无论有无GnRH,瘦素均可诱导垂体细胞产生并分泌LH和FSH。诱导垂体细胞产生促性腺激素最多的瘦素浓度为10⁻¹⁰ mol/L,这与青春期的生理浓度相同。瘦素可能参与青春期的启动。还可以推测,瘦素可能是排卵障碍的一个原因,不仅在体重减轻时,在体重增加时也是如此。