Estrogen receptor (ESR) 2 partially offsets the absence of ESR1 in gonadotropes of pituitary-specific Esr1 knockout female mice

José E. Sánchez-Criado, Kourtney Trudgen, Yolanda Millán, Alfonso Blanco, José Monterde, José C. Garrido-Gracia, Ana Gordon, Rafaela Aguilar, Juana Martín De Las Mulas, Che Myong Ko

Research output: Contribution to journalArticle

Abstract

Estrogen receptor 1 and 2 (ESR1 and 2) mediate estrogen (E) action on gonadotrope function. While much is known about the effects of ESR1 on the gonadotrope, there is still some controversy regarding the effects of ESR2. To investigate the role of ESR2 in the gonadotrope, 45-day-old female mice of two different genotypes were used: wild type (WT) and pituitary (gonadotropes and thyrotropes)-specific Esr1 knockout (KO). All mice were ovariectomized (OVX) and 15 days later injected over 3 days with 2.5 μg 17β-estradiol (E 2), 0.2 mg of the selective ESR1 or 2 agonists, propylpyrazole triol and diarylpropionitrile, respectively, or 0.1 ml oil. The day after treatment, anterior pituitary glands were dissected out for evaluation of gonadotrope ultrastructural morphology and pituitary immunohistochemical expression of progesterone receptor (Pgr (Pr)). Blood was collected and serum LH levels were assessed. Activation of ESR1 in WT mice resulted in the following: i) uterine ballooning and vaginal cornification, ii) negative feedback on LH secretion, iii) increased number of homogeneous (functional) gonadotropes, and iv) pituitary Pgr expression (35.9±2.0% of pituitary cells). Activation of ESR1 in KO mice induced normal uterine, vaginal, and LH secretion responses, but failed to increase the number of functional gonadotropes, and induced significantly lower Pgr expression (21.0±3.0% of pituitary cells) than in WT mice. Whilst activation of ESR2 had no significant effects in WT mice, it doubled the number of functional gonadotropes exhibited by KO mice injected with oil. It is concluded that E2 exerted its action in KO mouse gonadotropes via ESR2.

Original languageEnglish (US)
Pages (from-to)549-558
Number of pages10
JournalReproduction
Volume143
Issue number4
DOIs
StatePublished - Apr 1 2012
Externally publishedYes

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Estrogen Receptor beta
Knockout Mice
Oils
Anterior Pituitary Gland
Estrogen Receptor alpha
Progesterone Receptors
Estradiol
Estrogens
Genotype
Serum

ASJC Scopus subject areas

  • Reproductive Medicine
  • Embryology
  • Endocrinology
  • Obstetrics and Gynecology
  • Cell Biology

Cite this

Sánchez-Criado, J. E., Trudgen, K., Millán, Y., Blanco, A., Monterde, J., Garrido-Gracia, J. C., ... Ko, C. M. (2012). Estrogen receptor (ESR) 2 partially offsets the absence of ESR1 in gonadotropes of pituitary-specific Esr1 knockout female mice. Reproduction, 143(4), 549-558. https://doi.org/10.1530/REP-11-0214

Estrogen receptor (ESR) 2 partially offsets the absence of ESR1 in gonadotropes of pituitary-specific Esr1 knockout female mice. / Sánchez-Criado, José E.; Trudgen, Kourtney; Millán, Yolanda; Blanco, Alfonso; Monterde, José; Garrido-Gracia, José C.; Gordon, Ana; Aguilar, Rafaela; De Las Mulas, Juana Martín; Ko, Che Myong.

In: Reproduction, Vol. 143, No. 4, 01.04.2012, p. 549-558.

Research output: Contribution to journalArticle

Sánchez-Criado, JE, Trudgen, K, Millán, Y, Blanco, A, Monterde, J, Garrido-Gracia, JC, Gordon, A, Aguilar, R, De Las Mulas, JM & Ko, CM 2012, 'Estrogen receptor (ESR) 2 partially offsets the absence of ESR1 in gonadotropes of pituitary-specific Esr1 knockout female mice', Reproduction, vol. 143, no. 4, pp. 549-558. https://doi.org/10.1530/REP-11-0214
Sánchez-Criado JE, Trudgen K, Millán Y, Blanco A, Monterde J, Garrido-Gracia JC et al. Estrogen receptor (ESR) 2 partially offsets the absence of ESR1 in gonadotropes of pituitary-specific Esr1 knockout female mice. Reproduction. 2012 Apr 1;143(4):549-558. https://doi.org/10.1530/REP-11-0214
Sánchez-Criado, José E. ; Trudgen, Kourtney ; Millán, Yolanda ; Blanco, Alfonso ; Monterde, José ; Garrido-Gracia, José C. ; Gordon, Ana ; Aguilar, Rafaela ; De Las Mulas, Juana Martín ; Ko, Che Myong. / Estrogen receptor (ESR) 2 partially offsets the absence of ESR1 in gonadotropes of pituitary-specific Esr1 knockout female mice. In: Reproduction. 2012 ; Vol. 143, No. 4. pp. 549-558.
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abstract = "Estrogen receptor 1 and 2 (ESR1 and 2) mediate estrogen (E) action on gonadotrope function. While much is known about the effects of ESR1 on the gonadotrope, there is still some controversy regarding the effects of ESR2. To investigate the role of ESR2 in the gonadotrope, 45-day-old female mice of two different genotypes were used: wild type (WT) and pituitary (gonadotropes and thyrotropes)-specific Esr1 knockout (KO). All mice were ovariectomized (OVX) and 15 days later injected over 3 days with 2.5 μg 17β-estradiol (E 2), 0.2 mg of the selective ESR1 or 2 agonists, propylpyrazole triol and diarylpropionitrile, respectively, or 0.1 ml oil. The day after treatment, anterior pituitary glands were dissected out for evaluation of gonadotrope ultrastructural morphology and pituitary immunohistochemical expression of progesterone receptor (Pgr (Pr)). Blood was collected and serum LH levels were assessed. Activation of ESR1 in WT mice resulted in the following: i) uterine ballooning and vaginal cornification, ii) negative feedback on LH secretion, iii) increased number of homogeneous (functional) gonadotropes, and iv) pituitary Pgr expression (35.9±2.0{\%} of pituitary cells). Activation of ESR1 in KO mice induced normal uterine, vaginal, and LH secretion responses, but failed to increase the number of functional gonadotropes, and induced significantly lower Pgr expression (21.0±3.0{\%} of pituitary cells) than in WT mice. Whilst activation of ESR2 had no significant effects in WT mice, it doubled the number of functional gonadotropes exhibited by KO mice injected with oil. It is concluded that E2 exerted its action in KO mouse gonadotropes via ESR2.",
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