THE PRIMATE OVARY CONTAINS A POPULATION OF CATECHOLAMINERGIC NEURON-LIKE CELLS EXPRESSING NERVE GROWTH-FACTOR RECEPTORS

The ovary of humans and nonhuman primates is innervated by sympathetic and sensory neurons of the peripheral nervous system. Recent studies demonstrated that the density of the sympathetic innervation to the rh esus monkey ovary is developmentally regulated, with adult density bei ng attained around the time of puberty. In the present study, we used an immunocytochemical approach to obtain insights into the cell-cell s ignaling mechanisms that may contribute to the functional maintenance of this innervation. Because sympathetic neurons of the peripheral ner vous system require target-derived neurotropins for their survival and function, experiments were conducted to determine if one of the recep tors recognized by neurotropins is expressed in fibers innervating the primate ovary. A monoclonal antibody to the human low-affinity nerve growth factor (NGF) receptor, termed p75 NGFR because of its molecular weight, demonstrated the presence of this receptor in nerve fibers in nervating the ovarian vasculature, interstitial tissue, and developing follicles of the gland. In addition, as shown in rodents, p75 NGFR im munoreactivity was detected in nonneuronal, endocrine cells of the ova ry, specifically the thecal cell layer of developing follicles. Unexpe ctedly, however, the monkey ovary was also found to contain a network of small p75 NGFR immunoreactive cells distributed throughout the ovar ian medulla and cortex. These cells, identified as such by confocal mi croscopy, had a neural-like appearance and displayed both neurofilamen t and neuron-specific enolase immunoreactivity. They appeared to be de nsely interconnected and were seen innervating the ovarian vasculature , the thecal cell layer of follicles, and, occasionally, primordial fo llicles. Double immunohistochemical procedures demonstrated that a sub population of these intraovarian, p75 NGFR-bearing neuron-like cells a re catecholaminergic, as determined by their immunoreactivity to antib odies to tyrosine hydroxylase, the rate-limiting enzyme in catecholami ne biosynthesis. RNA blot hybridization revealed the presence of p75 N GFR messenger RNA in the monkey ovary, thus demonstrating the ability of the gland to synthesize the receptors. These results demonstrate th at the primate ovary contains an intrinsic network of neuron-like cell s. Because such a neuronal network has not been detected in rodents or other nonprimate species, it would appear that its presence in the pr imate ovary may have evolutionary significance.