Recently published work and emerging research efforts have suggested that the olfactory system is intimately linked with the endocrine systems that regulate or modify energy balance. Although much attention has been focused on the parallels between taste transduction and neuroendocrine controls of digestion due to the novel discovery of taste receptors and molecular components shared by the tongue and gut, the equivalent body of knowledge that has accumulated for the olfactory system, has largely been overlooked. During regular cycles of food intake or disorders of endocrine function, olfaction is modulated in response to changing levels of various molecules, such as ghrelin, orexins, neuropeptide Y, insulin, leptin, and cholecystokinin. In view of the worldwide health concern regarding the rising incidence of diabetes, obesity, and related metabolic disorders, we present a comprehensive review that addresses the current knowledge of hormonal modulation of olfactory perception and how disruption of hormonal signaling in the olfactory system can affect energy homeostasis.

Food odours are major determinants for food choice; their detection is influenced by nutritional status. Among different metabolic signals, insulin plays a major role in food intake regulation. The aim of the present study was to investigate a potential role of insulin in the olfactory mucosa (OM), using ex vivo tissues and in vitro primary cultures. We first established the expression of insulin receptor (IR) in rat olfactory mucosa. Transcripts of IR-A and IR-B isoforms, as well as IRS-1 and IRS-2, were detected in OM extracts. Using immunocytochemistry, IR protein was located in olfactory receptor neurones, sustentacular and basal cells and in endothelium of the lamina propria vessels. Moreover, the insulin binding capacity of OM was quite high compared to that of olfactory bulb or liver. Besides the main pancreatic insulin source, we demonstrated insulin synthesis at a low level in the OM. Interestingly 48 h of fasting, leading to a decreased plasmatic insulin, increased the number of IR in the OM. Local insulin concentration was also enhanced. These data suggest a control of OM insulin system by nutritional status. Finally, an application of insulin on OM, aiming to mimic postprandial insulin increase, reversibly decreased the amplitude of electro-olfactogramme responses to odorants by approximately 30%. These data provide the first evidence that insulin modulates the most peripheral step of odour detection at the olfactory mucosa level.

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Trophoblastin, an antiluteolytic component from the embryo, was identified in the ewe by the means of intrauterine injections of homogenates from trophoblasts at 14--16 days pregnancy. Homogenates from embryos and their membranes at 21--23 days pregnancy did not extend the life of the corpus luteum, suggesting that trophoblastin synthesis occurs for only a short period. The trophoblastin was thermolabile (80 degrees C for 30 min) and inactivated by pronase. Treatment of ewes with oCS, hCG, and extracts of 120-day placentae did not affect the time of luteolysis. The protein appears to be insoluble at pH 7 or 8, but to dissolve readily at pH 9.6. After injection of homogenates or extracts from 15--16-day-old trophoblasts, the initial CL were maintained for more than 1 month in most cyclic recipient ewes. Surgical removal of embryos at 21--23 days resulted in luteal maintenace for more than 1 month in over 50% of the operated animals. All the maintained CL were secretory although their average weight was about one-half of that CL of normal pregnancy, suggesting the existence of complementary luteotrophic placental factors. The uteri of most of these pseudopregnant ewes were distended with a clear, sterile fluid.

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Obesity is associated with chronic food intake disorders and binge eating. Food intake relies on the interaction between homeostatic regulation and hedonic signals among which, olfaction is a major sensory determinant. However, its potential modulation at the peripheral level by a chronic energy imbalance associated to obese status remains a matter of debate. We further investigated the olfactory function in a rodent model relevant to the situation encountered in obese humans, where genetic susceptibility is juxtaposed on chronic eating disorders. Using several olfactory-driven tests, we compared the behaviors of obesity-prone Sprague-Dawley rats (OP) fed with a high-fat/high-sugar diet with those of obese-resistant ones fed with normal chow. In OP rats, we reported 1) decreased odor threshold, but 2) poor olfactory performances, associated with learning/memory deficits, 3) decreased influence of fasting, and 4) impaired insulin control on food seeking behavior. Associated with these behavioral modifications, we found a modulation of metabolism-related factors implicated in 1) electrical olfactory signal regulation (insulin receptor), 2) cellular dynamics (glucorticoids receptors, pro- and antiapoptotic factors), and 3) homeostasis of the olfactory mucosa and bulb (monocarboxylate and glucose transporters). Such impairments might participate to the perturbed daily food intake pattern that we observed in obese animals.

A critical step in establishment of human pregnancy is the invasion of the uterus wall by the extravillous cytotrophoblast (EVCT), a process regulated by multiple autocrine and paracrine factors. Hormones belonging to the GH/prolactin family are expressed at the maternofetal interface. Because they are involved in cell motility in various models, we examined the possible regulatory role of human placental GH (hPGH) in EVCT invasiveness. By using an in vitro invasion model, we found that EVCT isolated from first-trimester chorionic villi and cultured on Matrigel secreted hPGH and expressed human GH receptor (hGHR). These data were confirmed by in situ immunohistochemistry. EVCT expressed the full-length and truncated forms of hGHR, and the Janus kinase-2/signal transducer and activator of transcription factor-5 signaling pathway was activated in EVCT by hPGH treatment. Strong hPGH and hGHR expression was observed when EVCT invaded Matrigel and moved through the pores of the filter on which they were cultured. hPGH stimulated EVCT invasiveness, and this effect was inhibited by a Janus kinase-2 inhibitor. Interestingly, hPGH was more efficient than pituitary GH in stimulating EVCT invasiveness. These results offer the first evidence for a placental role of hPGH and suggest an autocrine/paracrine role of hPGH in the regulation of trophoblast invasion.