Hormonal contraception can suppress natural antimicrobial gene transcription in human endometrium.
OBJECTIVE
To determine the effect of hormonal contraception with a combined oral contraceptive pill and levonorgestrel intrauterine system on the expression of the natural antimicrobials secretory leukocyte protease inhibitor, beta-defensins 1 and 2, and granulysin in human endometrium.


METHODS
Observational study.


METHODS
Day case ward in a department of obstetrics and gynecology.


METHODS
Fifty seven women undergoing gynecologic procedures for benign conditions; 24 received no contraception for more than 3 months, 20 received a combined oral contraceptive for more than 3 months, and 13 wore a levonorgestrel intrauterine system for more than 3 months.


METHODS
Endometrial samples were collected from all women. Messenger RNA was extracted and quantitative polymerase chain reaction was used to investigate expression of secretory leukocyte protease inhibitor, beta-defensin 1, beta-defensin 2, and granulysin. Immunohistochemistry for secretory leukocyte protease inhibitor was performed.


RESULTS
All antimicrobials varied cyclically. The level of secretory leukocyte protease inhibitor was maximal in the late secretory and menstrual phase, beta-defensin 1 in the mid secretory phase, granulysin in the late secretory phase, and beta-defensin 2 in the menstrual phase. Use of a combined oral contraceptive or levonorgestrel intrauterine system use decreased messenger RNA expression of beta-defensin 1 and 2 and granulysin but not secretory leukocyte protease inhibitor.


CONCLUSIONS
Endogenous and exogenous sex-steroid hormones, in the form of a combined oral contraceptive or levonorgestrel intrauterine system, influence gene transcription of secretory leukocyte protease inhibitor, beta-defensin 1, beta-defensin 2, and granulysin in the endometrium.
Fleming
Diana C
DC
Human Reproductive Sciences Unit, Medical Research Council, Academic Centre, Edinburgh, United Kingdom. d.fleming@hrsu.mrc.ac.uk
King
Anne E
AE
Williams
Alistair R W
AR
Critchley
Hilary O D
HO
Kelly
Rodney W
RW
D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis* / Q000235:genetics; D001706:Biopsy; D003277:Contraceptives, Oral, Combined / Q000494:pharmacology*; D004717:Endometrium / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D007434:Intrauterine Devices; D016912:Levonorgestrel / Q000008:administration & dosage* / Q000494:pharmacology; D008597:Menstrual Cycle / Q000187:drug effects / Q000378:metabolism; D014176:Protein Biosynthesis; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins / Q000235:genetics; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000187:drug effects; D023083:beta-Defensins / Q000096:biosynthesis* / Q000235:genetics
D000945:Antigens, Differentiation, T-Lymphocyte; D003277:Contraceptives, Oral, Combined; C075005:GNLY protein, human; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D023083:beta-Defensins; D016912:Levonorgestrel; D012313:RNA