PARENT SESSION

(157) THE ELASMOBRANCH EPIGONAL-OVARIAN COMPLEX (EOC): REGULATION OF LEUKOCYTE TURNOVER BY SEX HORMONES.

Lutton, Bram ¹, Callard, Ian¹, ¹ Boston University, Boston, MA

ABSTRACT- In mammals, it is well known that sex hormones affect both the innate and acquired immune systems by up- or down-regulation of the cells and factors they produce. It has been shown that, in general, estrogens hypersensitize the immune system while androgens and progestins are thought to down-regulate immune function. The cartilaginous fish (sharks, skates, and rays) offer a novel approach to the study of endocrine-immune interactions. These are the only species in which the gonads are directly associated with an autonomous immune tissue, the epigonal organ. Furthermore, the constant turnover of immune cells, via regulation of leukocyte proliferation and apoptosis, is critical for maintenance of homeostasis. To test whether sex hormones have an effect on cellular turnover of the epigonal organ, we utilized immunohistochemical (IHC) techniques to investigate apoptosis (TUNEL) and proliferation (proliferating cell nuclear antigen, PCNA Ab) of this unique leukopoietic tissue from reproductively active (RA) vs. non-reproductively active (NRA) little skates (Leucoraja erinacea). IHC analyses showed that that RA animals exhibited greater apoptosis than NRA animals, while the opposite was true for proliferation, suggesting a potential effect of sex steroids. We then used in vitro experiments to test the effects of 10^-5M estradiol (E₂), progesterone (P₄), testosterone (T), and dexamethasone (Dex) on apoptosis and proliferation of epigonal leukocytes. Immunocytochemical labeling of cultured cells with BrdU Ab and caspase-3 Ab, and fragmented DNA isolation in agarose gels, demonstrated a significant influence of sex steroids on immune cell turnover. This is the first study to demonstrate a reproductive endocrine-immune interaction in an elasmobranch species. It is likely that this association also illustrates, at least in part, how these animals have survived for over 450 million years to become the oldest extant jawed vertebrates. Investigation of this novel association offers potential for helping to understand the mechanisms behind both physiological and pathophysiological influences of sex hormones in higher vertebrates, including humans. Supported by NICHD training grant fellowship (HD 007387-12) to BVL and NIEHS (ES 07381) to IPC.

KEY WORDS: hormones, immune, ovary, fishes