The Effect Of Combination Of Adrenocorticotropic Hormone And Dexamethasone On Adrenal Cortex Of Rabbit

The secretion of glucocorticoids(GCs)is controlled by hypothalamicpituitary-adrenal axis(HPAA).Exogenous glucocorticoids inhibit the secretion of corticotropin-releasing hormone(CRH)and adrenocorticotropic hormone(ACTH).Long-term use of GC induces insufficient secretion of GC and adrenal atrophy.ACTH could be injected for GC-alternative therapy.But the ACTH preparations from pituitary glands of cows,sheep and pigs,usually caused allergic reactions.The feedback inhibition of GC on adrenal cortex may be antagonized by ACTH,and allergic reactions caused by ACTH preparations can also be reduced by immunosuppressant GC.Objective: To explore the new method of exogenous GC treatment by GC combined with ACTH application.Methods: The rabbits were divided randomly into normal control group(NC group),dexamethasone group(DEXA group),low dose of dexamethasone combined with high dose of ACTH(group HDLA),and high dose of dexamethasone combined with low dose of ACTH(group LDHA).The extent of apoptosis of anterior pituitary cells and adrenal cortex atrophy was evaluated by using TUNEL staining and immunohistochemical techniques.By using immunohistochemistry and reverse transcriptase polymerase chain reaction(RT-PCR)technique,the expression level of ACTH receptor in adrenal cortex was evaluated.The concentration of corticosterone in plasma was determined by enzyme-linked immunosorbent assay(ELISA).Results:1 HE staining of zona fasciculata of adrenal cortex: The zona fasciculata atrophied in DEXA group(0.35 mm± 0.05mm)and HDLA group(0.37 mm± 0.04 mm),and was significantly thinner than that in NC group(0.72 mm± 0.08 mm)(P<0.01);zona fasciculata atrophy atrophy is not obvious in LDHA group(0.69 mm± 0.13 mm)(P>0.05).2 Anterior pituitary cell apoptosis: No visible apoptotic cells were seen in NC group;the apoptotic rate of anterior pituitary cells in DEXA group(13.5%±1.3%)and HDLA group(14.5%±2.2%)was significantly higher than that in LDHA group(3.7%±0.9%)(P<0.01).3 The expression of ACTH-R mRNA in adrenal cortex: The expression of ACTH-R mRNA in adrenal cortex in DEXA group(0.572±0.363)and HDLA group(0.634±0.177)was significantly lower than that in NC group(0.955±0.159)and LDHA group(0.935±0.166)(P<0.01).4 ACTH-R expression in adrenal cortex: The score of ACTH-R expression in adrenal cortex in DEXA group(4.333±1.241)and HDLA group(4.667±1.696)was significantly lower than that in NC group(9.667±2.155)(P<0.01).The score of ACTH-R expression in adrenal cortex in LDHA group(9.333±1.974)had no significant difference as compared with NC group(P>0.05).5 Determination of corticosterone: The secretion of corticosterone was significantly decreased in DEXA group(297±32)and HDLA group(278±30)(P<0.01).The concentration of corticosterone in plasma in LDHA group(386±41)had no significant difference as compared with NC group(402±41)(P>0.05).Conclusion:1 Relatively high dose of ACTH combined with low dose of GC can significantly reduce adrenal cortex atrophy and decrease secretory function and the expression of ACRH-R caused by long-term application of exogenous GC.2 Relatively high dose of ACTH combined with low dose of GC can significantly inhibit apoptosis of anterior pituitary cells induced by long-term application of exogenous GC.