title: Combined therapy with estrogen and testosterone eliminates the aggravating effect of estrogen replacement therapy on glomerular injury in hypercholesterolemic female Imai rats.
abstract: Hypercholesterolemic Imai rats spontaneously develop proteinuria and glomerulosclerosis, especially male animals. Ovariectomy aggravates glomerular injury in female Imai rats. However, estrogen replacement therapy did not abolish this aggravating effect of ovariectomy and rather aggravated glomerular injury with an increase in serum levels of lipids and growth hormone (GH). Whereas we have already reported that treatment with testosterone in addition to estrogen reduces GH levels and attenuates glomerular injury as compared with estrogen alone in male Imai rats, in the present study, to investigate whether increased GH levels may contribute to an enhancing effect of estrogen on glomerular injury, we treated ovariectomized female Imai rats with estrogen pulse testosterone. Group 1 was sham operated and group 2 was ovariectomized at 6 weeks of age. Groups 3, 4, and 5 were ovariectomized and received estrogen, testosterone, or estrogen plus testosterone, respectively. Body weight, urinary protein, and serum constituents were investigated every 4 weeks from 12 to 24 weeks of age. At 24 weeks of age, the rats were studied morphologically. Each treatment with estrogen or testosterone equally aggravated glomerular injury with an increase in both proteinuria and serum lipids with increased serum GH levels in estrogen-treated rats but without influencing GH levels in testosterone-treated rats; combined treatment with estrogen plus testosterone resulted in a reduction of both proteinuria and serum lipids to levels of the controls and attenuated glomerular injury to levels close to those of controls with a reduction of the elevated serum GH levels. These results suggest that increased GH levels may contribute to an enhancing effect of estrogen replacement therapy on glomerular injury and that testosterone, when administered to the estrogen-treated rats, seems to exert an attenuating effect on glomerular injury by suppressing GH levels.
authors.affiliation: Department of Internal Medicine, Saga Medical School, Saga, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Ikeda
authors.forename: T
authors.initials: T
authors.lastname: Sakemi
authors.forename: Y
authors.initials: Y
authors.lastname: Tomiyoshi
authors.forename: M
authors.initials: M
authors.lastname: Miyazono
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002784:Cholesterol / Q000097:blood; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D004967:Estrogens / Q000627:therapeutic use*; D005260:Female; D005923:Glomerulosclerosis, Focal Segmental / Q000473:pathology; D013006:Growth Hormone / Q000097:blood; D006937:Hypercholesterolemia / Q000150:complications*; D007674:Kidney Diseases / Q000139:chemically induced* / Q000150:complications / Q000188:drug therapy*; D007678:Kidney Glomerulus / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D011507:Proteinuria / Q000139:chemically induced; D051381:Rats; D011919:Rats, Inbred Strains; D013739:Testosterone / Q000627:therapeutic use*
chemical_list: D004967:Estrogens; D013739:Testosterone; D013006:Growth Hormone; D002784:Cholesterol