Myometrial effects of selective estrogen receptor modulators on estradiol-responsive gene expression are gene and

Yuhua Z Farnell1, Nancy H Ing

  • 1Department of Animal Science, Faculties of Genetics and Reproductive Biology, Texas A&M University, College Station, TX 77843-2471, USA.

Insights

Selective estrogen receptor modulators (SERMs) show varied effects on sheep myometrial gene expression. Different SERMs impact estrogen and progesterone receptor levels differently in distinct uterine layers.

Area of Science:

  • Reproductive Biology
  • Endocrinology
  • Pharmacology

Background:

  • Estrogen receptors (ER) play a crucial role in uterine function.
  • Selective estrogen receptor modulators (SERMs) are drugs that interact with ERs.
  • Understanding SERM effects on myometrium is vital for reproductive health.

Purpose of the Study:

  • To investigate the in vivo effects of specific SERMs on myometrial gene expression in ewes.
  • To determine if SERM actions differ between inner (IM) and outer (OM) myometrial layers.
  • To compare the effects of 4-OH-tamoxifen (Tam), GW 5638 (GW), and EM-800 (EM) on ER and progesterone receptor (PR) expression.

Main Methods:

  • Ovariectomized ewes received SERMs (Tam, GW, EM) or vehicle.
  • Some ewes received 17beta-estradiol (E2) treatment.
  • Gene expression analyzed via Northern blot and in situ hybridization.
  • Protein levels assessed using immunohistochemistry.

Main Results:

  • E2 increased ER, PR, and cyclophilin (CYC) gene expression in both IM and OM.
  • Tam increased ER mRNA in OM; EM also appeared to increase ER gene expression.
  • EM, Tam, and GW antagonized E2-induced PR gene expression, with varying layer specificity.
  • All SERMs antagonized E2-induced PR protein levels, particularly in the OM.
  • EM uniquely increased ER protein in myometrium, contrasting with endometrial effects.

Conclusions:

  • SERMs exhibit distinct, gene, and cell layer-specific effects on sheep myometrium.
  • SERM-ER interactions in the myometrium are complex and context-dependent.
  • These findings highlight differential SERM activity within uterine layers, impacting reproductive physiology.

Related Concept Videos

Internal Receptors01:31

Internal Receptors

Many cellular signals are hydrophilic and therefore cannot pass through the plasma membrane. However, small or hydrophobic signaling molecules can cross the hydrophobic core of the plasma membrane and bind to internal, or intracellular, receptors that reside within the cell. Many mammalian steroid hormones use this mechanism of cell signaling, as does nitric oxide (NO) gas.
Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the addition of a...