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Abstract

Prenatal exposure to dexamethasone alters Leydig cell steroidogenic capacity in immature and adult rats (PDF) (HTML) 
Page,Kathleen Creed; Sottas,Chantal M.; Hardy,Matthew P.
Journal of Andrology 22(6): 973-980
Publication date: 2001

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This study examines the effects of prenatal exposure to dexamethasone (DEX)on postnatal testosterone production in male rats. Pregnant female ratswere treated on gestation days 14-19 with DEX (100 microg/kg body weightper day; n = 9) or vehicle (n = 9). Results show that 35-day-old maleoffspring from DEX-treated pregnant females (n = 42) had decreased levelsof serum testosterone (45.6% lower, P < .05) compared with controloffspring (n = 43), although serum luteinizing hormone (LH) levels were notsignificantly altered. These findings suggest that a direct programming ofdeveloping gonadal cells occurs in response to high levels of maternalglucocorticoid. Indeed, testosterone production was significantly reducedin Leydig cells isolated from immature offspring of DEX-treated pregnantfemales compared with controls (48.3%, P < .001), and LH stimulation ofthese cells did not compensate for the lowered steroidogenic capacity. Thehypothalamic-pituitary-adrenal axis was also affected, because significantreductions in both serum adrenocorticotropic hormone (ACTH; 26.2%, P <.001) and corticosterone (CORT; 32.3%, P < .001) were measured inDEX-exposed immature male offspring. In contrast, adult male offspring fromDEX-treated dams had significantly higher levels of serum ACTH (39.2%, P<. 001) and CORT (37.8%, P < .001). These same animals had higherserum testosterone (31.6%, P < or = .05) and a significant reduction inserum LH (30.8%, P < .001). Moreover, Leydig cells isolated from theseadult offspring exhibited an increased capacity for testosteronebiosynthesis under basal (38.6%, P < .001) and LH-stimulated conditions(33.5%, P < .001). In summary, sustained changes in steroidogeniccapacity were observed in male rats exposed to high levels ofglucocorticoid during prenatal development. More specifically, DEX exposurein utero perturbed Leydig cell testosterone production in both pubertal andadult rats.

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