Increased propensity for amyloidogenesis in male mice

S. Shtrasburg^1,5, M. Pras^1,5, M. Dulitzky^2,5, C. Pariente², R. Gal^3,5, A. Mor^4,5, A. Livneh^1,5

¹Heller Institute of Medical Research and ²Department of Obstetrics and Gynecology, Sheba Medical Center, Tel-Hashomer; ³Department of Pathology, Rabin Medical Center, Golda Campus, Hasharon Hospital, Petach-Tikva; ⁴Department of Medicine, Meir General Hospital, Kfar Saba; and ⁵Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel. 

ABSTRACT
Background
The male sex is a risk factor for reactive amyloidogenesis in several disease entities. Environmental, socioeconomic or genetic factors may underlie this male preponderance. This study was aimed at discovering whether male sex predisposes to reactive amyloidosis also in mice and to elucidate some of the hormonal associations of this risk. 

Methods
Male and female Swiss mice were subjected to an established amyloid induction protocol and the amount of their splenic amyloid was determined and compared. The effect of estrogen, progesterone, testosterone and adrenalin on amyloidogenesis was studied in both sexes by administering these hormones during amyloid induction and comparing the amount of splenic amyloid of the study mice with the control mice which received the amyloid induction protocol alone. 

Results
Amyloid deposition appeared to be more abundant in male mice. This gender difference was not associated with any of the 3 sex hormones tested. Despite an expected increment, adrenalin caused an attenuation of amyloid deposition. 

Conclusions
The preferential expression of reactive amyloidosis in male mice seems to be unrelated to the common sex hormones. Increased production of other hormones such as adrenalin, or perhaps an augmented susceptibility to their effect, may cause gender differences by suppressing female amyloidogenesis. Our study favors the hypothesis of genetic predisposition as the mechanism leading to sex differences in amyloidogenesis. Further validation of our findings in gonadal ablated models and other amyloid induction protocols is warranted.

Key words
Amyloid A, amyloid enhancing factor, animal model, adrenalin, sex hormones.

Please address correspondence to: Shmuel Shtrasburg, BSc, Heller Institute of Medical Research, Sheba Medical Center, Tel Hashomer 52621, Israel. 
E-mail: shmuels@sheba.health.gov.il

Clin Exp Rheumatol 2004; 22: 421-426.
© Copyright Clinical and Experimental Rheumatology 2004.