Early studies revealed that ovarian histamine secretion is acutely regulated by luteinizing hormone. The cellular source(s) of histamine in the ovary are unknown. Recently, my lab has described in hamster, human and several other species numerous mast cells surrounding blood vessels that enter and exit the ovary; numerous mast cells were also observed in the ovarian hilum but not in the follicular portion. This novel discovery has led to the proposed studies using the cyclic hamster.
The first aim i s to describe the cellular localization and distribution of histidine decarboxylase (HDC) in the ovary and uterus throughout the estrous cycle using immunohistochemical methods with antibodies to HDC. Although mast cells are a primary source of histamine synthesis other cellular types such as basophils and eosinophils may also produce histamine.
The second aim i s to determine which hormones (pituitary gonadotropins, steroids and prostaglandins) alter ovarian and uterine blood flow, degranulation of mast cells and release of histamine into circulation. Hormones will be injected intra-arterially into proestrous hamsters. At various intervals after injection ovarian blood flow will be determined using radioactive microspheres; one ovary-blood vessel complex and uterine horn and sera will be analyzed for histamine (bioassay and HPLC), steroids and prostaglandins. The remaining ovary and its blood vessel complex and uterine horn will be stained with Toluidine blue in order to assess the effects of the hormones on the pattern of mast cell degranulation. Mast cell degranulation will be classified into 3 categories: no degranulation - less than 5 granules released from the cell body; moderate degranulation - 5-15 granules released; extensive degranulation - greater than 15 granules released.
The third aim will determine whether the hormones that alter degranulation do so by binding directly to mast cells; this will be assessed by autoradiography and in vitro binding of radiolabeled hormones to isolated ovarian and peritoneal mast cells. Also, isolated mast cells will be tested for their ability to release histamine in response to gonadotropins, steroids and prostaglandins in vitro.
The fourth aim will correlate follicular development with mast degranulation, histamine levels and ovarian blood flow. Mast cells may be a major factor regulating ovarian blood flow and thus causally related to follicular development. Future plans are to determine the location of ovarian histamine receptors, the effects of H1 and H2 agonists and antagonists on ovarian blood flow and follicular development in animal and human models.
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