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. 2022 Nov 25;23(23):14757.
doi: 10.3390/ijms232314757.

Kelulut Honey Regulates Sex Steroid Receptors in a Polycystic Ovary Syndrome Rat Model

Datu Agasi Mohd Kamal  1   2 , Siti Fatimah Ibrahim  1 , Azizah Ugusman  1 , Mohd Helmy Mokhtar  1
Affiliations

Kelulut Honey Regulates Sex Steroid Receptors in a Polycystic Ovary Syndrome Rat Model

Datu Agasi Mohd Kamal et al. Int J Mol Sci. .

Abstract

Reproductive and metabolic anomalies in polycystic ovary syndrome (PCOS) have been associated with the dysregulation of sex steroid receptors. Kelulut honey (KH) has been shown to be beneficial in PCOS-induced rats by regulating folliculogenesis and the oestrus cycle. However, no study has been conducted to evaluate KH's effect on sex steroid receptors in PCOS. Therefore, the current study examined the effects of KH, metformin, or clomiphene alone and in combination on the mRNA expression and protein distribution of androgen receptor (AR), oestrogen receptor α (ERα), oestrogen receptor β (ERβ), and progesterone receptor (PR) in PCOS-induced rats. The study used female Sprague-Dawley rats, which were treated orally with 1 mg/kg/day of letrozole for 21 days to develop PCOS. PCOS-induced rats were then divided and treated orally for 35 days with KH, metformin, clomiphene, KH + metformin, KH+ clomiphene and distilled water. In this study, we observed aberrant AR, ERα, ERβ and PR expression in PCOS-induced rats compared with the normal control rats. The effects of KH treatment were comparable with clomiphene and metformin in normalizing the expression of AR, ERα, and ERβ mRNA. However, KH, clomiphene and metformin did not affect PR mRNA expression and protein distribution. Hence, this study confirms the aberrant expression of sex steroid receptors in PCOS and demonstrates that KH treatment could normalise the sex steroid receptors profile. The findings provide a basis for future clinical trials to utilize KH as a regulator of sex steroid receptors in patients with PCOS.

Keywords: PCOS; androgen receptor; honey; oestrogen receptors; progesterone receptor.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Effects of KH on AR mRNA expression. NC: normal control; PCOS: untreated PCOS; M: PCOS + metformin; C: PCOS + clomiphene; KH: PCOS + 1 g/kg/day of Kelulut honey; KH + M: PCOS + 1 g/kg/day of Kelulut honey + metformin; KH + C: PCOS + 1 g/kg/day of Kelulut honey + clomiphene. * p < 0.05 significance compared to the normal control group, # p < 0.05 significance compared to the untreated PCOS group, n = 6 per treatment group.
Figure 2
Figure 2
(A) Representative images of AR protein distribution and (B) quantitative analysis of AR protein staining intensity in the treatment groups. The antibody-binding site of AR is marked by the dark brown stain present in granulosa cell nuclei of primary follicles, antral follicles and preovulatory follicles. NC: normal control; PCOS: untreated PCOS; M: PCOS + metformin; C: PCOS + clomiphene; KH: PCOS + 1 g/kg/day of Kelulut honey; KH + M: PCOS + 1 g/kg/day of Kelulut honey + metformin; KH + C: PCOS + 1 g/kg/day of Kelulut honey + clomiphene. Scale bar = 100 μm. Magnification 200× and 400×. * p < 0.05 significance compared to the normal control group, # p < 0.05 significance compared to the untreated PCOS group. n = 6 per group.
Figure 3
Figure 3
Effects of KH on (A) ERα and (B) ERβ mRNA expression. NC: normal control; PCOS: untreated PCOS; M: PCOS + metformin; C: PCOS + clomiphene; KH: PCOS + 1 g/kg/day of Kelulut honey; KH + M: PCOS + 1 g/kg/day of Kelulut honey + metformin; KH + C: PCOS + 1 g/kg/day of Kelulut honey + clomiphene. * p < 0.05 significance compared to the normal control group, # p < 0.05 significance compared to the untreated PCOS group, n = 6 per treatment group.
Figure 4
Figure 4
(A) Representative images of ERα protein distribution and (B) quantitative analysis of ERα protein staining intensity in the treatment groups. The antibody-binding site of ERα is marked by the dark brown stain that is present in granulosa cells and theca cells of primary follicles, antral follicles, and preovulatory follicles. NC: normal control; PCOS: untreated PCOS; M: PCOS +metformin; C: PCOS + clomiphene; KH: PCOS + 1 g/kg/day of Kelulut honey; KH + M: PCOS + 1 g/kg/day of Kelulut honey + metformin; KH + C: PCOS + 1 g/kg/day of Kelulut honey + clomiphene. Scale bar = 50 μm. Magnification 100×, n = 6 per group. * p < 0.05 significance compared to the normal control group, # p < 0.05 significance compared to the untreated PCOS group. n = 6 per group.
Figure 5
Figure 5
(A) Representative images of ERβ protein distribution and (B) quantitative analysis of ERβ protein staining intensity in the treatment groups. The antibody-binding site of ERβ is marked by the dark brown stain present in the granulosa cells and theca cells of primary follicles, antral follicles, and preovulatory follicles. NC: normal control; PCOS: untreated PCOS; M: PCOS + metformin; C: PCOS + clomiphene; KH: PCOS + 1 g/kg/day of Kelulut honey; KH + M: PCOS + 1 g/kg/day of Kelulut honey + metformin; KH + C: PCOS + 1 g/kg/day of Kelulut honey + clomiphene. Scale bar = 50 μm and 100 μm. Magnification 100×, n = 6 per group. * p < 0.05 significance compared to the normal control group, # p < 0.05 significance compared to the untreated PCOS group. n = 6 per group.
Figure 6
Figure 6
Effects of KH on mRNA expression of PR. NC: normal control; PCOS: untreated PCOS; M: PCOS + metformin; C: PCOS + clomiphene; KH: PCOS + 1 g/kg/day of Kelulut honey; KH + M: PCOS + 1 g/kg/day of Kelulut honey + metformin; KH + C: PCOS + 1 g/kg/day of Kelulut honey + clomiphene. * p < 0.05 significance compared to the normal control group, n = 6 per treatment group.
Figure 7
Figure 7
Effect of KH on PR protein distribution. The antibody-binding site of PR is marked by the dark brown stain that presents only in the oviduct and not in the ovary. NC: normal control; PCOS: untreated PCOS; M: PCOS + metformin; C: PCOS + clomiphene; KH: PCOS + 1 g/kg/day of Kelulut honey; KH + M: PCOS + 1 g/kg/day of Kelulut honey + metformin; KH + C: PCOS + 1 g/kg/day of Kelulut honey + clomiphene. Scale bar = 50 μm and 100 μm. Magnification 40×, n = 6 per group.
Figure 8
Figure 8
The illustration depicts the study design. AR: androgen receptor; ER: oestrogen receptor; PR: progesterone receptor; qPCR: quantitative polymerase chain receptor; IHC: immunohistochemistry.
See this image and copyright information in PMC

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References

    1. Swaroop A., Jaipuriar A.S., Gupta S.K., Bagchi M., Kumar P., Preuss H.G., Bagchi D. Efficacy of a Novel Fenugreek Seed Extract (Trigonella foenum-graecum, Furocyst) in Polycystic Ovary Syndrome (PCOS) Int. J. Med. Sci. 2015;12:825–831. doi: 10.7150/ijms.13024. - DOI - PMC - PubMed
    1. Teede H., Deeks A., Moran L. Polycystic ovary syndrome: A complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan. BMC Med. 2010;8:41. doi: 10.1186/1741-7015-8-41. - DOI - PMC - PubMed
    1. Escobar-Morreale H.F. Polycystic ovary syndrome: Definition, aetiology, diagnosis and treatment. Nat. Rev. Endocrinol. 2018;14:270. doi: 10.1038/nrendo.2018.24. - DOI - PubMed
    1. Azziz R., Carmina E., Chen Z., Dunaif A., Laven J.S., Legro R.S., Lizneva D., Natterson-Horowtiz B., Teede H.J., Yildiz B.O. Polycystic ovary syndrome. Nat. Rev. Dis. Prim. 2016;2:16057. doi: 10.1038/nrdp.2016.57. - DOI - PubMed
    1. Gupta M., Singh D., Toppo M., Priya A., Sethia S., Gupta P. A cross sectional study of polycystic ovarian syndrome among young women in Bhopal, Central India. Int. J. Community Med. Public Health. 2018;5:95–100. doi: 10.18203/2394-6040.ijcmph20175603. - DOI