Parotid gland tissue is able partially to assume pituitary functions under the influence of hypothalamic factors: in vivo and in vitro studies

Abstract

To test whether salivary tissue can secrete pituitary hormones, female Sprague-Dawley rats were hypophysectomized (hypox) and the following were transplanted to the sella turcica: parotid gland (group 3, n=33), adrenal gland (group 4, n=30), muscle (group 5, n=24). Group 2 (n=21) had the sella turcica filled with dentist's cement. In addition a group of rats (group 1, n=22) remained intact as controls. All groups were followed for 8 months. Daily vaginal smears showed normal cyclicity in controls and constant dioestrus in all hypox groups. Blood samples, taken once every 30 days before and after LHRH stimulation, showed significantly lower (P<0·001) plasma LH values in all hypox groups compared with controls. In group 3, a gradual and significant increase (P<0·05) was observed in the LH response to LHRH in parallel with a partial recovery of oestrous smears. No LH modification was observed in the other hypox groups. Plasma prolactin (PRL) levels were also very low in all hypox groups and were unaltered throughout the study. At the end of the experiments, half the animals were killed by decapitation and the hypothalamic-pituitary areas carefully dissected, homogenized and analysed for LH and PRL content. The remaining animals were perfused with 4% paraformaldehyde to obtain fixing of the whole body tissues. Hypothalamic and transplant areas were carefully dissected, frozen, cut and submitted to immunochemical procedures. LH content in the graft of group 3 animals was markedly (P<0·001) lower than in the control pituitary, but significantly higher (P<0·05) than in the other hypox groups. Immunochemistry showed LH and PRL positive cells in the graft of group 3 animals, whereas neither positive cells, nor LH content were observed in the parotid gland in situ. Experiments were completed with in vitro cultures of parotid glands in the presence or absence (controls) of synthetic hypothalamic hormones or rat hypothalamic extracts. After 1·5 weeks of culture, a significantly higher LH concentration (P<0·05) was observed in the wells treated with synthetic hypothalamic hormones (216 46 pg/ml vs 41 6 pg/ml in controls). When hypothalamic extracts were used, the LH levels increased more markedly (1834 190 pg/ml vs 36 6 pg/ml in controls) and those values were maintained during 3 weeks of culture. Immunostaining of these cultures showed a positive LH reaction in the epithelial cells found in the hypothalamic extract-treated wells. Both in vivo and in vitro studies confirm the transdifferentiation of parotid gland tissue to pituitary hormone-producing cells under hypothalamic influence.

Pre‐morbid morphological conditions of the human pituitary

“…Less known is the experimental data on the functional transformation of implanted salivary gland tissue, which became able to produce growth hormones, only when implanted with contact in the hypothalamus, 14,15 None of our cases had positive immunohistochemical reaction to any pituitary hormones, neither was any pituitary cell metaplasia of the heterotopic salivary gland cells morphologically confirmed.…”

Salivary gland tissues and derived primary and metastatic neoplasms: unusual pitfalls in the work-up of sellar lesions. A systematic review

“…This may be explained by pre-existing seromucous glands from the primitive oral cavity remaining in the Rathke’s pouch during migration and persisting during postnatal life [ 17 ], similar to ectopic pituitary tissue reported at various locations along its migratory path, including the roof of the nasopharynx [ 53 ]. Experimental studies also suggest that Rathke’s pouch components may occasionally differentiate into salivary and adenohypophyseal tissues during organogenesis [ 54 ] and that parotid gland tissue may trans-differentiate into pituitary hormone-producing cells under the influence of hypothalamic factors [ 55 ]. Embryological development would thus explain why NNESG are found close to the posterior pituitary lobe and sometimes within RCC’s wall [ 16 – 18 ].…”

GH gene expression in the submaxillary gland in normal and Ames dwarf mice

“…Rat parotid gland cells in culture, submitted to hypothalamic extracts or synthetic hypothalamic hormones, were able to synthesize and secrete some pituitary hormones including luteinizing hormone (LH), prolactin, and growth hormone (GH) (Tresguerres et al 1999a, Fernandez et al 1994. In these experiments, the effect was less marked when synthetic factors were used, probably indicating the existence of unknown enhancers in the crude hypothalamic extract.…”