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Trends in Endocrinology and Metabolism 7 — PNAS 99 — PNAS 98 — Cancer Research 61 — Sign in Create account. Author guidelines Submit now Reasons to publish Ethical policy Open-access policy Publication charges Author resource centre. Advanced Search Help. FSH and testosterone signaling in Sertoli cells in Reproduction. Correspondence should be addressed to W H Walker; Email: walkerw pitt. Free access. Download PDF. Check for updates. Get Permissions. Abstract Testosterone and follicle-stimulating hormone FSH are required to obtain full reproductive potential.
Introduction Male fertility and the process of spermatogenesis are dependent upon the somatic Sertoli cells to produce factors that are required by developing germ cells reviewed in Sharpe , Griswold Sertoli cell ontogeny and FSH signaling During the last four days of gestation fetal days Cyclical regulation of the FSH receptor in the adult In the adult rat seminiferous tubules, spermatogenesis occurs in a cyclical fashion such that, within any one region of the tubule, spermatogonial stem cells divide approximately every 12 days.
Phospholipase A 2 PLA 2 pathway FSH through the activation of phospholipase A 2 PLA 2 leads to the release of the arachadonic acid second messenger and its subsequent metabolism to prostoglandin E 2 and other eicosanoids that function as intracellular and extracellular signals. During embryonic development, androgens direct cells to read specific segments of the DNA that hold instructions for how to build these organs.
AR has the potential to regulate many different genes and thus many different behaviors For example, AR activation by testosterone in some cell types can lead to increased expression of the FADS1 gene , which increases production of important fats 2.
In prostate cells, AR regulates other genes that are important for cell duplication—a helpful behavior during embryonic development when the body needs to generate more cells to build organs. This diagram helps illustrate the concept. On the left, the AR protein can be represented by the green orb. After activation, it binds to the DNA and promotes gene expression. Of course, this is a simplification—in the real world, the process is more complex and may include many proteins.
Imagine transcription factors as a football coach in charge of the offense. What would happen if you accidently put them in charge of the defense? One of the more well known misuses of AR occurs during the development and progression of prostate cancer Cancer can develop for numerous reasons, but there are some common hallmarks that cause a cell to make the transformation from normal to cancerous 7.
One of those hallmarks is overcoming protective barriers that normally prevent cells from duplicating themselves. This is a complex process that can happen in different ways, but a common way involves misuse of important transcription factors—like AR—which are then able to alter cell behavior.
Through various means, prostate cancer cells may cause excessive activity from the AR protein Recall that, during development, testosterone binds with the AR protein and causes prostate cells to grow and duplicate themselves 1. Hormones can affect cells directly through intracellular hormone receptors or indirectly through plasma membrane hormone receptors.
The hormone is called a first messenger and the cellular component is called a second messenger. G-proteins activate the second messenger cyclic AMP , triggering the cellular response. Response to hormone binding is amplified as the signaling pathway progresses. Cellular responses to hormones include the production of proteins and enzymes and altered membrane permeability. Skip to content Chapter The Endocrine System.
Learning Objectives By the end of this section, you will be able to: Explain how hormones work Discuss the role of different types of hormone receptors. Intracellular Hormone Receptors. Figure Upon hormone binding, the receptor dissociates from the heat shock protein and translocates to the nucleus. In the nucleus, the hormone-receptor complex binds to a DNA sequence called a hormone response element HRE , which triggers gene transcription and translation.
The corresponding protein product can then mediate changes in cell function. Plasma Membrane Hormone Receptors. Summary Hormones cause cellular changes by binding to receptors on target cells. Exercises A new antagonist molecule has been discovered that binds to and blocks plasma membrane receptors. What effect will this antagonist have on testosterone, a steroid hormone?
It will block testosterone from binding to its receptor. It will block testosterone from activating cAMP signaling. It will increase testosterone-mediated signaling. It will not affect testosterone-mediated signaling. What effect will a cAMP inhibitor have on a peptide hormone-mediated signaling pathway? It will prevent the hormone from binding its receptor.
It will prevent activation of a G-protein. It will prevent activation of adenylate cyclase. It will prevent activation of protein kinases.
Name two important functions of hormone receptors.
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