Abstract
The membrane progesterone receptors (mPRα, mPRβ, mPRγ, mPRδ and mPRε) are known to mediate rapid nongenomic progesterone functions in different cell types. However, the functions of these receptors in the pituitary have not been reported to date. In the present study, we show that the expression of mPRα was the highest among the mPRs in the rat anterior pituitary gland. Immunostaining of mPRα was detected in somatotrophs, gonadotrophs and lactotrophs. Interestingly, 63% of mPRα-positive cells within the pituitary were lactotrophs, suggesting that mPRα is involved in controlling prolactin (PRL) secretion in the pituitary. To test this hypothesis, rat pituitaries were incubated (1 hour) with either progesterone (P4) or the mPRα-specific agonist Org OD 02-0. PRL secretion was then measured by radioimmunoassay. The results of this experiment revealed that both P4 and Org OD 02-0 decreased PRL secretion. Moreover, the results from the GH3 cell line (CCL-82.1) showed that P4 and Org OD 02-0 inhibited PRL release, although the nuclear PR agonist R5020 was ineffective. Our investigation of the cellular mechanisms behind mPRα activity indicated that both P4 and Org OD 02-0 decreased cAMP accumulation, whereas R5020 was ineffective. In addition, the Org OD 02-0-effect on PRL release was blocked by pretreatment with pertussis toxin, an inhibitor of Go/Gi proteins. Because transforming growth factor (TGF)β1 is a potent inhibitor of PRL secretion in lactotrophs, we lastly evaluated whether TGFβ1 was activated by progesterone and whether this effect was mediated by mPRα. Our results showed that P4 and Org OD 02-0, but not R5020, increased active TGFβ1 levels. This effect was not observed when cells were transfected with mPRα-small interfering RNA. Taken together, these data provide new evidence suggesting that mPRα mediates the progesterone inhibitory effect on PRL secretion through both decreases in cAMP levels and activation of TGFβ1 in the lactotroph population.
Original language | English (US) |
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Article number | e12614 |
Journal | Journal of Neuroendocrinology |
Volume | 30 |
Issue number | 9 |
DOIs | |
State | Published - Sep 2018 |
Funding
Funding information This work was supported by the Agencia Nacional de Promoción Científica y Técnica, Buenos Aires, Argentina (grant PICT N2136 to GDT), René Barón Foundation (to GDT), Williams Foundation (to GDT), HEB Endowed Chair in Marine Science (to PT). The prolactin RIA kit was generously provided by the National Institute of Diabetes and Digestive and Kidney Diseases National Hormone and Pituitary Program (Dr A. Parlow). This work was supported by the Agencia Nacional de Promoción Científica y Técnica, Buenos Aires, Argentina (grant PICT N2136 to G?T), René Barón Foundation (to G?T), Williams Foundation (to G?T), HEB Endowed Chair in Marine Science (to PT).
Keywords
- lactotrophs
- membrane progesterone receptors
- pituitary
- prolactin
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Endocrinology
- Endocrine and Autonomic Systems
- Cellular and Molecular Neuroscience