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Target Cell Response to Hormones01:22

Target Cell Response to Hormones

Hormones intricately bind to receptors on the surface or within target cells, initiating a cascade of cellular responses.
Notably, the cellular response can be regulated by altering the number of receptors expressed in the cell. For example, prolonged exposure to elevated hormone levels results in a gradual decline or down-regulation in the number of receptors for that specific hormone on the cell surface. Conversely, in response to low hormone levels, cells may use up-regulation, producing an...
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Generation of Multicellular Human Primary Endometrial Organoids
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16α-hydroxyprogesterone: origin, biosynthesis and receptor interaction.

Karl-Heinz Storbeck1, Pieter Swart, Donita Africander

  • 1Department of Biochemistry, University of Stellenbosch, Stellenbosch 7602, South Africa.

Molecular and Cellular Endocrinology
|November 25, 2010
PubMed
Summary
This summary is machine-generated.

16α-hydroxyprogesterone (16-OHPROG), a metabolite of progesterone, binds to human progesterone receptors (hPR). This finding clarifies the role of 16-OHPROG in reproductive function, acting as an agonist for both hPR-A and hPR-B.

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Area of Science:

  • Endocrinology
  • Steroid Metabolism
  • Molecular Biology

Background:

  • Progesterone (PROG) metabolism by CYP17A1 produces 17α-hydroxyprogesterone (17-OHPROG) and 16α-hydroxyprogesterone (16-OHPROG).
  • 16-OHPROG is a stable metabolite with an unclear physiological role, despite its presence in human serum and urine.
  • The enzyme cytochrome P450 17α-hydroxylase/17,20-lyase (CYP17A1) catalyzes PROG hydroxylation.

Purpose of the Study:

  • To review the production of 16-OHPROG by human CYP17A1.
  • To elucidate the role of the amino acid Alanine at position 105 (Ala105) in CYP17A1's 16α-hydroxylation of PROG.
  • To investigate the interaction of 16-OHPROG with human progesterone receptors (hPR) due to its putative link to reproductive function.

Main Methods:

  • Review of CYP17A1 catalysis of PROG.
  • Analysis of the structural role of Ala105 in 16α-hydroxylation.
  • In vitro investigation of 16-OHPROG binding to hPR-A and hPR-B isoforms.

Main Results:

  • The review details PROG metabolism by CYP17A1, emphasizing Ala105's significance in 16α-hydroxylation.
  • 16-OHPROG was demonstrated to bind to both hPR-A and hPR-B.
  • 16-OHPROG acts as an agonist for both hPR-A and hPR-B receptors.

Conclusions:

  • 16-OHPROG is a functional ligand for human progesterone receptors.
  • This study provides the first evidence of 16-OHPROG binding to and activating hPR-A and hPR-B.
  • The findings contribute to understanding the physiological role of 16-OHPROG in reproductive processes.