Presence of Sex Steroid‐Metabolizing Enzymes in the Olfactory Mucosa of Rats

Abstract

Although several lines of evidence have suggested that sex steroids influence olfaction, little is known about the cellular basis of steroid-metabolizing enzymes in the olfactory system. Thus, we aimed to examine gene expression and immunolocalization of four sex steroid-metabolizing enzymes in the olfactory mucosa (OM) of albino rats; steroid side chain-cleaving enzyme (P450scc), 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD-1), 17β-HSD type 2 (17β-HSD-2), and aromatase. P450scc is known to catalyze conversion from cholesterol to pregnenolone. 17β-HSD-1 catalyzes conversion from estrone to estradiol, and 17β-HSD-2 does the reverse. Aromatase catalyzes the conversion from testosterone to estradiol-17β. Messenger (m) RNAs of all four enzymes mentioned above were detected in the OM. Western blot analysis demonstrated that P450scc, 17β-HSD-1, and 17β-HSD-2 were detected in the OM. Immunoreactivity for these three enzymes was observed in sustentacular cells of the olfactory epithelium and acinar cells of Bowman's glands. Immunoelectron microscopy analysis demonstrated immunoreactivity for P450scc in mitochondria, and for 17β-HSD-1 and 17β-HSD-2 in the well-developed smooth endoplasmic reticulum and myeloid bodies of the sustentacular cells. The present study suggests that sustentacular cells and acinar cells of the Bowman's glands in the rat OM express at least three of the steroid-metabolizing enzymes, that is, P450scc 17β-HSD-1, and 17β-HSD-2, and de novo synthesis of estradiol takes place in the OM. Anat Rec, 300:402-414, 2017. © 2016 Wiley Periodicals, Inc.

The role of metals in mammalian olfaction of low molecular weight organosulfur compounds

“…In addition to action by OBPs and ODEs, this aqueous protein solution can modify the characteristics of the olfactory message through selective concentration and partitioning of components of mixtures. 22c,d In the context of this review, and as will be discussed below, it is significant that nasal mucus of mice has been found to contain 40 μM levels of copper ions. In humans, levels of Zn, Cu, Mg and Ca in nasal mucus are 14, 16, 1554 and 5303 μg/dL, respectively, and 92, 106, 2150 and 9820 μg/L in human serum, respectively.…”

“…1,22a These differences could be attributed to events occurring prior to OR-ligand interaction, e.g., perireceptor events . 22b Perireceptor events are defined as those biophysical and biochemical events involving odorant molecules taking place before the odorants reach the ORs in the extracellular space in the proximity of OSNs, for example in the 5–30 mm thick, continuously flowing nasal mucus in vertebrates in which the OSN cilia are immersed. 22c,d These interactions involve both odorant-binding proteins (OBPs) as well as odorant-degrading enzymes (ODEs) present in nasal mucus 22 .…”

“…Lipocalins are carrier proteins in aqueous media for hydrophobic ligands, including odorants, and may also have a role in clearance of odorants. 1,22c,d The ODE, also abundant in nasal mucus, protect the OE, lungs and brain against potentially dangerous inhaled xenobiotics. Enzymes involved in biotransformation of xenobiotics include cytochrome P450 monooxygen-ases, aldehyde dehydrogenases, aldehyde oxidases, aldehyde reductases, carbonic anhydrases, carboxyl esterases, and various transferases and transporters, with activities comparable if not higher than that measured in the liver.…”

“…In studies involving mice, Nagashima and Touhara 22e demonstrated, using both pharmacological and behavioral tests, that aldehyde and ester odorants are targets of metabolic enzymes secreted into the mouse nasal mucus, resulting in their oxidative and hydrolytic conversions to the corresponding acids and alcohols, respectively. As a consequence, the ultimate perception is of a mixture of the original odorant and its metabolic derivatives, rather than of a single species of odorant molecule.…”

“…Furthermore, odorant metabolites may be more soluble than the parent odorants, and may reach high concentrations in the mucus bathing the ORNs. 22f Nasal mucus constitutes a barrier odorants need to cross to reach the ORs. In addition to action by OBPs and ODEs, this aqueous protein solution can modify the characteristics of the olfactory message through selective concentration and partitioning of components of mixtures.…”