Johnson K M, Hughes F M, Fong Y Y, Mathur R S, Williamson H O, Gorospe W C
Department of Obstetrics and Gynecology, Medical University of South Carolina, Charleston 29425.
Am J Reprod Immunol. 1994 Mar-Apr;31(2-3):163-8. doi: 10.1111/j.1600-0897.1994.tb00861.x.
The localization and biological effects of atrial natriuretic peptide (ANP) are not limited to cardiac tissue but extend to a number of extra-atrial tissues and organs, including the ovary. The objective of the present study was to determine the effects of ANP on granulosa cell steroidogenesis. Hence, the direct effects of ANP on the production of progesterone, 20 alpha-hydroxpregn-4-en-3-one (20 alpha-OH-P), and estrogen by undifferentiated and differentiated rat ovarian granulosa cells were examined in vitro.
Undifferentiated granulosa cells obtained from the ovaries of diethylstilbestrol-primed, immature rats were treated with increasing doses (10(-12) to 10(-6) M) of rANP for 48 h.
ANP evoked a two- and threefold increase in progesterone and 20 alpha-OH-P production relative to untreated controls, respectively. Increasing doses of ANP in combination with porcine FSH (125 ng/well) resulted in a biphasic response in progesterone production above FSH-treated controls. Specifically, a maximal inhibition of 35% in progesterone production was achieved at 10(-9) M ANP, followed by a stimulation to levels comparable with FSH-stimulated controls at higher doses examined. Increasing doses of ANP evoked a twofold increase in FSH-stimulated 20 alpha-OH-P production over respective controls. Following pretreatment of granulosa cells with FSH for 48 h to evoke differentiation, ANP caused a significant dose-dependent inhibition in basal progesterone production that resulted in a 76% suppression at the highest dose examined. In contrast, ANP evoked a 2.8-fold increase in 20 alpha-OH-P production when compared with controls. Finally, in FSH-stimulated differentiated granulosa cells, ANP evoked a threefold increase in progesterone production and a 65% inhibition in 20 alpha-OH-P production. ANP exerted no significant effects on estrogen production by either undifferentiated or differentiated granulosa cells in the presence or absence of FSH.
These data demonstrate that ANP can modulate directly progestin steroidogenesis in both undifferentiated and differentiated rat ovarian granulosa cells in vitro and, therefore, may play an important role in granulosa cell differentiation and follicular maturation.
心房利钠肽（ANP）的定位和生物学效应并不局限于心脏组织，而是扩展到许多心房外的组织和器官，包括卵巢。本研究的目的是确定ANP对颗粒细胞类固醇生成的影响。因此，在体外研究了ANP对未分化和分化的大鼠卵巢颗粒细胞产生孕酮、20α-羟孕-4-烯-3-酮（20α-OH-P）和雌激素的直接作用。
从己烯雌酚预处理的未成熟大鼠卵巢中获得未分化的颗粒细胞，用递增剂量（10^(-12)至10^(-6)M）的重组ANP（rANP）处理48小时。
与未处理的对照组相比，ANP分别使孕酮和20α-OH-P的产生增加了两倍和三倍。递增剂量的ANP与猪促卵泡素（FSH，125 ng/孔）联合使用，导致孕酮产生相对于FSH处理的对照组出现双相反应。具体而言，在10^(-9)M ANP时，孕酮产生最大抑制率达到35%，随后在更高剂量下刺激至与FSH刺激的对照组相当的水平。递增剂量的ANP使FSH刺激的20α-OH-P产生相对于各自对照组增加了两倍。在用FSH预处理颗粒细胞48小时以诱导分化后，ANP导致基础孕酮产生显著的剂量依赖性抑制，在最高检测剂量下抑制率达76%。相比之下，与对照组相比，ANP使20α-OH-P产生增加了2.8倍。最后，在FSH刺激的分化颗粒细胞中，ANP使孕酮产生增加了三倍，使20α-OH-P产生抑制了65%。在有无FSH的情况下，ANP对未分化或分化的颗粒细胞产生雌激素均无显著影响。
这些数据表明，ANP在体外可直接调节未分化和分化的大鼠卵巢颗粒细胞中的孕激素类固醇生成，因此可能在颗粒细胞分化和卵泡成熟中起重要作用。
