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Involvement of glucocorticoid and mineralocorticoid receptors in lipid accumulation and depressed G6PD activity in the livers of rats treated with postpartum oral estrogen-progestin

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Abstract

Postpartum contraception is an important step for preventing closely spaced pregnancy. Combined oral contraceptive (COC) has been linked to cardiometabolic disturbances. We therefore hypothesized that postpartum oral estrogen-progestin use induces hepatic lipid accumulation that is associated with glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) activation via adenosine deaminase (ADA)/xanthine oxidase (XO)/uric acid (UA)-dependent pathway. Female Wistar rats weighing 130–150 g were mated to achieve timed pregnancy and delivery. Twenty-four (24) dams were randomly assigned to receive vehicle (po), COC (1.0 μg ethinylestradiol and 5.0 μg levonorgestrel; po), COC with GR blockade (mifepristone; 80.0 mg/kg; po) and COC with MR blockade (spironolactone; 0.25 mg/kg; po) daily between 3rd and 11th week postpartum. Data showed that postpartum COC resulted in glucose dysregulation, increased visceral adiposity, liver weight, plasma corticosterone, aldosterone, circulating and hepatic free fatty acid (FFA), triglyceride (TG), adenosine deaminase (ADA), uric acid production, lactate production, and oxidative marker injury. On the other hand, G6PD-dependent antioxidant defenses were depressed by postpartum COC. However, these effects were attenuated by GR or MR blockade. Our data demonstrate that enhanced G6PD-dependent antioxidant defenses and suppressed ADA/XO/UA pathway in the liver by GR or MR blockade improves glucose dysregulation and hepatic TG accumulation induced by postpartum COC. This study implies a plausible involvement of GR and MR via defective G6PD-dependent antioxidant barrier and increased activity of ADA/XO/UA pathway in postpartum COC-induced hepatic lipid accumulation.

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Acknowledgements

This study was supported by the Association of African Universities grant (AAU/2017/2018) and International Society of Hypertension (ISH) through the ISH grant for mentors (2017). The authors appreciate the technical support from the HOPE Cardiometabolic Research Team, Ilorin, Nigeria.

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Authors and Affiliations

  1. HOPE Cardiometabolic Research Team and Department of Physiology, College of Health Sciences, University of Ilorin, P.M.B. 1515, Ilorin, 240001, Nigeria

    Olufunto O. Badmus & Lawrence A. Olatunji

  2. Department of Public Health, Kwara State University, Malete, Nigeria

    Olufunto O. Badmus

Authors
  1. Olufunto O. Badmus
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  2. Lawrence A. Olatunji
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Contributions

OLA conceived and designed the research. BOO conducted experiments. OLA contributed new reagents and analytical kits. BOO and OLA analyzed and interpreted data. BOO and OLA drafted the manuscript. BOO and OLA read and approved the final manuscript.

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Correspondence to Lawrence A. Olatunji.

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The investigation was conducted in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals and was approved by the University ethical review committee, with protocol identification number UERC/ASN/2016/486, and every effort was made to minimize both the number of animals used and their suffering.

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The authors declare that they have no conflict of interest.

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Badmus, O.O., Olatunji, L.A. Involvement of glucocorticoid and mineralocorticoid receptors in lipid accumulation and depressed G6PD activity in the livers of rats treated with postpartum oral estrogen-progestin. Naunyn-Schmiedeberg's Arch Pharmacol 392, 913–924 (2019). https://doi.org/10.1007/s00210-019-01634-1

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  • DOI: https://doi.org/10.1007/s00210-019-01634-1

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