Oocytes are a source of catecholamines in the primate ovary: Evidence for a cell–cell regulatory loop

Abstract

Catecholamines, thought to derive from the extrinsic innervation of the ovary, participate in the regulation of ovarian development and mature gonadal function. Recently, intraovarian neurons containing tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis, were described in the ovary of nonhuman primates. We now show that the primate ovary expresses both the genes encoding TH and dopamine ␤-hydroxylase (DBH), the key enzymes in norepinephrine (NE) biosynthesis. Ovarian neurons were identified as a site of TH and DBH gene expression, and surprisingly, oocytes were identified as an exclusive site of DBH synthesis. Oocytes contain neither TH mRNA nor protein, indicating that they are unable to synthesize dopamine (DA). They did, however, express a DA transporter gene identical to that found in human brain. The physiological relevance of this transporter system and DBH in oocytes was indicated by the ability of isolated oocytes to metabolize exogenous DA into NE. Isolated follicles containing oocytes-but not those from which the oocytes had been removed-responded to DA with an elevation in cAMP levels; this elevation was prevented by propranolol, a ␤-adrenoreceptor antagonist. The results suggest that oocytes and somatic cells are linked by a neuroendocrine loop consisting of NE synthesized in oocytes from actively transported DA and cAMP produced by somatic follicular cells in response to NE-induced ␤-adrenoreceptor activation.All three major catecholamines used as transmitters by sympathetic neurons of the peripheral nervous system are present in the mammalian ovary (1, 2). Among them, norepinephrine (NE) is the most abundant (1, 3, 4). A variety of experimental approaches have demonstrated that NE, recognized by specific receptors of the ␤ 2 -adrenergic subtype, stimulates ovarian steroidogenesis on its own and facilitates the stimulatory effect of gonadotropins on steroid production (5-7). NE also promotes follicular development (8-10). In contrast to this body of information, very little is known about the potential contribution(s) of dopamine (DA) to ovarian physiology. In one of the few studies on the subject (11), a stimulatory effect of DA on human granulosa cell steroidogenesis was blocked by propranolol, a ␤-adrenoreceptor antagonist, indicating that the effect of the catecholamine was indirect and most likely mediated by NE.It is commonly assumed that catecholamines reach the ovary exclusively via its extrinsic sympathetic innervation (12). However, ovarian denervation reduces, but does not eliminate, the content of NE in the gland (13), implying the existence of an additional source of catecholamine synthesis. That this source may be intrinsic to the ovary has been suggested by the identification of neuronal cell bodies containing immunoreactive tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis, in the ovary of nonhuman primates (14). Whether this is the only, or the more important, intragonadal source of catecholamines in the primate ...

Neuronal Elements in the Testis of the Rhesus Monkey: Ontogeny, Characterization and Relationship to Testicular Cells

“…Moreover, the gene for TH is expressed in the monkey testis and similar cells were found in the ovary of the monkey [30, 31], lending further support for the existence of these cells at least in primates. This cell type may act alone and/or in concert with the extrinsic sympathetic innervation of the testis.…”

“…The testicular distribution of NF-200, TH, NPY, synaptosomal associated protein of 25 kDa (SNAP-25) and mast cells tryptase was examined in monkey testes using an ABC-immunohistochemical method as described previously [31, 34, 35]. Specific antibodies were employed (mouse monoclonal antibody anti-NF-200: Boehringer Mannheim Inc., Indianapolis, Ind., USA; dilution 1:50; rabbit polyclonal antibody anti-TH: Chemicon International Inc., Temecula, Calif., USA, dilution 1:400; rabbit polyclonal antibody anti-NPY: Peninsula Laboratories Inc., Belmont, Calif., USA, dilution 1:70,000; mouse monoclonal antibody directed against a synaptosomal associated protein of 25 kDa, SNAP-25: Sternberger Monoclonals Inc., Baltimore, Md., USA, dilution 1:500; mouse monoclonal antibody antitryptase: Dako, Hamburg, Germany, dilution 1:50).…”

Stress Hormone–Mediated Invasion of Ovarian Cancer Cells

“…Stress can also increase tissue catecholamine levels in the ovary via increased sympathetic activity, which has been shown to trigger precystic follicles (47 -50). However, in addition to the sympathetic innervation, the primate ovary contains the endogenous enzymatic machinery necessary for catecholamine biosynthesis (51). As a result, ovarian tissue levels of catecholamines can substantially exceed those in plasma (22).…”

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