title: Receptor-mediated gonadotropin action in the ovary. Action of cytoskeletal element-disrupting agents on gonadotropin-induced steroidogenesis in rat luteal cells.
abstract: The role of the cellular cytoskeletal system of microtubules and microfilaments on gonadotropin-stimulated progesterone production by isolated rat luteal cells has been investigated. Exposure of luteal cells to human choriogonadotropin resulted in a stimulation of cyclic AMP (4-7-fold) and progesterone (3-4-fold) responses.l Incubation of cells with the microfilament modifier cytochalasin B inhibited the gonadotropin-induced steroidogenesis in a dose- and time-dependent manner. The effect of cytochalasin B on basal production of steroid was less pronounced. Cytochalasin B also inhibited the accumulation of progesterone in response to lutropin, cholera enterotoxin, dibutyryl cyclic AMP and 8-bromo cyclic AMP. The inhibition of steroidogenesis by cytochalasin B was not due to (a) inhibition of 125I-labelled human choriogonadotropin binding to luteal cells, (b) inhibition of gonadotropin-stimulated cyclic AMP formation or (c) a general cytotoxic effect and/or inhibition of protein biosynthesis. Cytochalasin D, like cytochalasin B, inhibited gonadotropin- and 8-bromo cyclic AMP-stimulated steroidogenesis. Although cytochalasin B also blocked the transport of 3-O-methyl-glucose into luteal cells, cytochalasin D was without such an effect. Increasing glucose concentration in the medium, or using pyruvate as an alternative energy source, failed to reverse the inhibitory effect of cytochalasin B. The anti-microtubular agent colchicine failed to modulate synthesis and release of progesterone by luteal cells in response to human choriogonadotropin. These studies suggest that the cellular microfilaments may be involved in the regulation of gonadotropin-induced steroidogenesis. In contrast, microtubules appear to be not directly involved in this process.
mesh_terms: D019325:3-O-Methylglucose; D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D003338:Corpus Luteum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D003571:Cytochalasin B / Q000494:pharmacology*; D003599:Cytoskeleton / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D008757:Methylglucosides / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D011374:Progesterone / Q000096:biosynthesis*; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism
chemical_list: D006063:Chorionic Gonadotropin; D008757:Methylglucosides; D011956:Receptors, Cell Surface; D019325:3-O-Methylglucose; D003571:Cytochalasin B; D011374:Progesterone; D000242:Cyclic AMP