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Luteinizing hormone secretion from wild-type and progesterone receptor knockout mouse anterior pituitary cells.
Endocrinology. 2001 Jul; 142(7):3108-15.E

Abstract

The progesterone receptor (PR) has a central role in the hypothalamo-pituitary events culminating in the preovulatory LH surge, and mice with genetically ablated PR provide a model for dissecting cellular pathways subserving this role. The aims of this study were to determine 1) whether the GnRH self-priming response and acute progesterone augmentation of secretagogue-stimulated LH secretion are present in cultured wild-type (WT) mouse pituitary cells, and 2) whether the PR is essential for self-priming by comparing the responses in PR knockout (PRKO) cells. Pituitary cells from ovariectomized WT or PRKO mice cultured +/- 17beta-estradiol (E(2)) for 3 days were challenged with hourly pulses of 1 nM GnRH or 54 mM K(+). A background of E(2) had no effect on the initial LH secretory response for either WT or PRKO cells. However, for subsequent GnRH pulses, E(2) was permissive for the GnRH self-priming response in WT cells. PRKO cells exhibited a blunted GnRH self-priming response. Exposure to progesterone for 90 min before secretagogue stimulation resulted in a modest (1.5-fold) augmentation of the LH response to GnRH but not K(+) pulses in WT cells; progesterone had no effect in PRKO cells. Unlike in the rat, the PR antagonists RU486 or ZK98299 failed to prevent potentiation of LH secretory responses to multiple GnRH pulses in WT cells. Although RU486 blocked progesterone augmentation of the initial GnRH pulse, it was ineffective in blocking progesterone's action after multiple GnRH pulses. In WT cells, 8- bromo-cAMP (8-Br-cAMP) was able to substitute for the GnRH priming pulse; 8-Br-cAMP also augmented GnRH-stimulated secretion in PRKO cells but less effectively. 8-Br-cAMP augmented K(+)-stimulated LH secretion in WT and PRKO cells equally. These results suggest that, although mouse gonadotropes show GnRH self-priming, they have adapted strategies different than rat cells for amplifying the GnRH signal as shown by the residual self-priming in PRKO cells, the modest or absent augmentation by acute progesterone of GnRH- or K(+)-stimulated secretion in WT cells, and the reduced ability of PR antagonists to interfere with GnRH self-priming and progesterone augmentation. We speculate that the adaptations could involve, at least in part, differences in the ratio of PR isoforms.

Authors+Show Affiliations

Department of Human Physiology, School of Medicine, University of California, Davis, Davis, California 95616, USA. jlturgeon@ucdavis.eduNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11416033

Citation

Turgeon, J L., and D W. Waring. "Luteinizing Hormone Secretion From Wild-type and Progesterone Receptor Knockout Mouse Anterior Pituitary Cells." Endocrinology, vol. 142, no. 7, 2001, pp. 3108-15.
Turgeon JL, Waring DW. Luteinizing hormone secretion from wild-type and progesterone receptor knockout mouse anterior pituitary cells. Endocrinology. 2001;142(7):3108-15.
Turgeon, J. L., & Waring, D. W. (2001). Luteinizing hormone secretion from wild-type and progesterone receptor knockout mouse anterior pituitary cells. Endocrinology, 142(7), 3108-15.
Turgeon JL, Waring DW. Luteinizing Hormone Secretion From Wild-type and Progesterone Receptor Knockout Mouse Anterior Pituitary Cells. Endocrinology. 2001;142(7):3108-15. PubMed PMID: 11416033.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Luteinizing hormone secretion from wild-type and progesterone receptor knockout mouse anterior pituitary cells. AU - Turgeon,J L, AU - Waring,D W, PY - 2001/6/21/pubmed PY - 2001/7/20/medline PY - 2001/6/21/entrez SP - 3108 EP - 15 JF - Endocrinology JO - Endocrinology VL - 142 IS - 7 N2 - The progesterone receptor (PR) has a central role in the hypothalamo-pituitary events culminating in the preovulatory LH surge, and mice with genetically ablated PR provide a model for dissecting cellular pathways subserving this role. The aims of this study were to determine 1) whether the GnRH self-priming response and acute progesterone augmentation of secretagogue-stimulated LH secretion are present in cultured wild-type (WT) mouse pituitary cells, and 2) whether the PR is essential for self-priming by comparing the responses in PR knockout (PRKO) cells. Pituitary cells from ovariectomized WT or PRKO mice cultured +/- 17beta-estradiol (E(2)) for 3 days were challenged with hourly pulses of 1 nM GnRH or 54 mM K(+). A background of E(2) had no effect on the initial LH secretory response for either WT or PRKO cells. However, for subsequent GnRH pulses, E(2) was permissive for the GnRH self-priming response in WT cells. PRKO cells exhibited a blunted GnRH self-priming response. Exposure to progesterone for 90 min before secretagogue stimulation resulted in a modest (1.5-fold) augmentation of the LH response to GnRH but not K(+) pulses in WT cells; progesterone had no effect in PRKO cells. Unlike in the rat, the PR antagonists RU486 or ZK98299 failed to prevent potentiation of LH secretory responses to multiple GnRH pulses in WT cells. Although RU486 blocked progesterone augmentation of the initial GnRH pulse, it was ineffective in blocking progesterone's action after multiple GnRH pulses. In WT cells, 8- bromo-cAMP (8-Br-cAMP) was able to substitute for the GnRH priming pulse; 8-Br-cAMP also augmented GnRH-stimulated secretion in PRKO cells but less effectively. 8-Br-cAMP augmented K(+)-stimulated LH secretion in WT and PRKO cells equally. These results suggest that, although mouse gonadotropes show GnRH self-priming, they have adapted strategies different than rat cells for amplifying the GnRH signal as shown by the residual self-priming in PRKO cells, the modest or absent augmentation by acute progesterone of GnRH- or K(+)-stimulated secretion in WT cells, and the reduced ability of PR antagonists to interfere with GnRH self-priming and progesterone augmentation. We speculate that the adaptations could involve, at least in part, differences in the ratio of PR isoforms. SN - 0013-7227 UR - https://www.unboundmedicine.com/medline/citation/11416033/Luteinizing_hormone_secretion_from_wild_type_and_progesterone_receptor_knockout_mouse_anterior_pituitary_cells_ L2 - https://academic.oup.com/endo/article-lookup/doi/10.1210/endo.142.7.8282 DB - PRIME DP - Unbound Medicine ER -