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18.24: Intracellular Hormone Receptors - Biology

18.24: Intracellular Hormone Receptors - Biology


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Lipid-derived (soluble) hormones such as steroid hormones diffuse across the membranes of the endocrine cell. In this way, the steroid hormone regulates specific cell processes as illustrated in Figure 1.

Practice Question

Heat shock proteins (HSP) are so named because they help refold misfolded proteins. In response to increased temperature (a “heat shock”), heat shock proteins are activated by release from the NR/HSP complex. At the same time, transcription of HSP genes is activated. Why do you think the cell responds to a heat shock by increasing the activity of proteins that help refold misfolded proteins?
[reveal-answer q=”23179″]Show Answer[/reveal-answer]
[hidden-answer a=”23179″]Proteins unfold, or denature, at higher temperatures.[/hidden-answer]

Other lipid-soluble hormones that are not steroid hormones, such as vitamin D and thyroxine, have receptors located in the nucleus. The hormones diffuse across both the plasma membrane and the nuclear envelope, then bind to receptors in the nucleus. The hormone-receptor complex stimulates transcription of specific genes.


Intracellular Receptor

F binds to an intracellular receptor , called the glucocorticoid receptor (GR) within target cells. GR, being expressed in almost all tissues, is a transcriptional regulatory factor consisting of three different domains: an N-terminal domain containing transactivation functions, a DNA-binding domain, and a ligand-recognition domain. Cortisol passes through the plasma membrane and binds to GR with high affinity within the cytoplasm. After dissociation from the interacted chaperone protein(s), GR-F complex tranaslocates into the nucleus, and then it binds to a specific DNA motif (hormone-response element, HRE) as a homodimer. The GR-F complex interacted with specific DNA induces or inhibits gene transcription [6] . While the genomic action of F is becoming better understood, little is known of the rapid non-genomic action of F. However, F may have an effect on prolactin release as a non-genomic function in fish cell culture systems [7] .


28.2 How Hormones Work

In this section, you will explore the following questions:

Connection for AP ® Courses

Much of the information in this section is an application of the material we explored in the Cell Communication chapter about cell communication and signaling pathways. Hormones are chemical signals (ligands) that mediate changes in target cells by binding to specific receptors. Even though hormones released by endocrine glands can travel long distances through the blood and come into contact with many different cell types, they only affect cells that possess the necessary receptors. Depending on the location of the receptor on the target cell and the chemical structure of the hormone, for example, whether or not it is lipid-soluble, hormones can mediate changes directly by binding to intracellular hormone receptors and modulating gene expression (transcription and translation), or indirectly by binding to cell surface receptors and simulating signaling pathways.

The hormone binds to its receptor like a key fits a lock. Because a lipid-derived hormone such as a steroid hormone can diffuse across the membrane of the target cell, they bind to intracellular receptors residing in the cytoplasm or in the nucleus. The cell signaling pathways induced by steroid hormones regulate specific genes by acting as transcription regulators. In turn, this affects the amount of protein produced. Lipid-derived hormones that are not steroids, for example, vitamin D and thyroxin, bind to receptors located in the nucleus of the target cell.

Because amino acid-derived hormones (with the exception of thyroxine) and polypeptide hormones are not lipid-soluble, they bind to plasma membrane hormone receptors located on the outer surface of the membrane. Unlike steroid hormones, they cannot act directly on DNA but activate a signaling pathway this triggers intracellular activity and carries out the specific effects associated with the hormone. The hormone that initiated the signaling pathway is called a first messenger. In the case of the epinephrine signaling pathway, binding of the amino acid-derived hormone epinephrine to its receptor activates a G-protein which, in turn, activates cAMP, a second messenger, ultimately resulting in a cellular response such as the conversion of glycogen to glucose.

Information presented and the examples highlighted in the section support concepts outlined in Big Idea 3 of the AP ® Biology Curriculum Framework. The AP ® Learning Objectives listed in the Curriculum Framework provide a transparent foundation for the AP ® Biology course, an inquiry-based laboratory experience, instructional activities, and AP ® exam questions. A learning objective merges required content with one or more of the seven science practices.

Big Idea 3 Living systems store, retrieve, transmit and respond to information essential to life processes.
Enduring Understanding 3.D Cells communicate by generating, transmitting and receiving chemical signals.
Essential Knowledge 3.D.3 Signal transduction pathways link signal reception with a cellular response.
Science Practice 1.5 The student can re-express key elements of natural phenomena across multiple representations in the domain.
Learning Objective 3.36 The student is able to describe a model that expresses the key elements of signal transduction pathways by which a signal is converted to a cellular response.

Hormones mediate changes in target cells by binding to specific hormone receptors. In this way, even though hormones circulate throughout the body and come into contact with many different cell types, they only affect cells that possess the necessary receptors. Receptors for a specific hormone may be found on many different cells or may be limited to a small number of specialized cells. For example, thyroid hormones act on many different tissue types, stimulating metabolic activity throughout the body. Cells can have many receptors for the same hormone but often also possess receptors for different types of hormones. The number of receptors that respond to a hormone determines the cell’s sensitivity to that hormone, and the resulting cellular response. Additionally, the number of receptors that respond to a hormone can change over time, resulting in increased or decreased cell sensitivity. In up-regulation, the number of receptors increases in response to rising hormone levels, making the cell more sensitive to the hormone and allowing for more cellular activity. When the number of receptors decreases in response to rising hormone levels, called down-regulation, cellular activity is reduced.

Receptor binding alters cellular activity and results in an increase or decrease in normal body processes. Depending on the location of the protein receptor on the target cell and the chemical structure of the hormone, hormones can mediate changes directly by binding to intracellular hormone receptors and modulating gene transcription, or indirectly by binding to cell surface receptors and stimulating signaling pathways.

Intracellular Hormone Receptors

Lipid-derived (soluble) hormones such as steroid hormones diffuse across the membranes of the endocrine cell. Once outside the cell, they bind to transport proteins that keep them soluble in the bloodstream. At the target cell, the hormones are released from the carrier protein and diffuse across the lipid bilayer of the plasma membrane of cells. The steroid hormones pass through the plasma membrane of a target cell and adhere to intracellular receptors residing in the cytoplasm or in the nucleus. The cell signaling pathways induced by the steroid hormones regulate specific genes on the cell's DNA. The hormones and receptor complex act as transcription regulators by increasing or decreasing the synthesis of mRNA molecules of specific genes. This, in turn, determines the amount of corresponding protein that is synthesized by altering gene expression. This protein can be used either to change the structure of the cell or to produce enzymes that catalyze chemical reactions. In this way, the steroid hormone regulates specific cell processes as illustrated in Figure 28.5.


Hormones circulate in the blood but their concentration can increase or decrease based on the requirement of the body. This is controlled by feedback mechanisms. These mechanisms control the secretion of endocrine glands by stimulating the hypothalamus, pituitary or both, which inturn governs the secretion of a particular hormone.

In positive feedback, the secretion of the hormone increases where as in negative feedback further secretion of hormone slows down. Feedback mechanisms are the key factors for maintaining homeostasis in our body.

Hormones are classified into three major groups as peptide hormones, steroid hormones and amino acid derived hormones based on their chemical structure.

Peptide hormones cannot cross the phospolipid cell membrane and bind to the receptors on the exterior cell surface. They are are transported to the golgi, which is the site of modification. It acts as a first messenger in the cell. Hormones on binding to their receptors do not enter the target cell but generate the production of second messengers such as cyclic AMP (c AMP), which in turn regulates cellular metabolism.

This is catalyzed by the enzyme adenylate cyclase. The interaction between the hormone at the surface and the effect brought out by cAMP within the cell is known as signaling cascade. At each step there is a possibility of amplification. (Figure 11.17)

  • One hormone molecule may bind to multiple receptor molecules before it is degraded.
  • Each receptor may activate several adenylate cyclases each of which make much cAMP.
  • Thus there is more signal after each step.

The actions of cAMP are terminated by phosphodiesterases. The effect of peptide hormones like insulin, glucagon, somatotropin are usually short lived because they work through second messenger system.

Steroid hormones can easily cross the cell membrane, and bind to their receptors, which are intracellular or intranuclear. Upon binding to the receptors, they pair up with another receptor – hormone complex (dimerize). This dimer can then bind to DNA and alter its transcription. (Figure 11.18)

The effect of steroid hormones such as aldosterone, oestrogen, FSH are long lived, as they alter the amount of mRNA and protein in a cell. Amino acid derived hormones are derived from one or two aminoacid with a few additional modifications. Thyroid hormone is synthesised from tyrosine and includes the addition of several iodine atoms.

Epinephrine an amino acid derivative may function through second messenger system like peptide hormones or they may actually enter the cell and function like steroid hormones.

Hormones activate target cells by diffusing through the plasma membrane of the target cells (lipid-soluble hormones) to bind a receptor protein within the cytoplasm of the cell, or by binding a specific receptor protein in the cell membrane of the target cell (water-soluble proteins).

There are two modes of hormonal action. A: Activation of cell-surface receptors and coupled second-messenger systems, with a variety of intracellular consequences.

Hormone levels are primarily controlled through negative feedback, in which rising levels of a hormone inhibit its further release. The three mechanisms of hormonal release are humoral stimuli, hormonal stimuli, and neural stimuli.

This type of mechanism is shown by lipid soluble hormones such as fatty acids and steroids that can easily pass through the plasma membrane. They possess intracellular receptors. The hormones bind to the target receptor that activates the enzymatic activity of the cell to bring about biochemical changes.

Mechanism of hormone action is not the same in all categories of hormones is a proteinaceous hormone, has large molecular weight and is insoluble in lipids, therefore, it cannot enter the target cell. Thus, it binds with the membrane bound receptor present on ovarian cell membrane.

The action involves secretion of by the thyroid gland into the circulation, uptake of target tissues, activation or inactivation of by deiodinase enzymes, binding of to nuclear receptors that act as ligand-regulated transcription factors, and regulation of expression of target genes.

What is the most common mechanism of hormone control? With negative feedback, the most common mechanism of hormone control, some feature of hormone action directly or indirectly inhibits further hormone secretion so that the hormone level returns to an ideal level or set point.

Hormones bind to specific proteins (hormone receptors) in the target tissues and produce effect on them. There are two types of receptors: membrane bound receptors (hormone receptors present on the cell membrane of the target cell) and intracellular receptors (receptors present inside the target cell).

The mechanism by which peptide hormones act upon specific target tissues to evoke characteristic functional responses is believed to be initiated by interaction with a highly special- ized portion of the plasma membrane, the so called hormone receptor site.


Review Questions

Consuming certain products cause a change in urine output. This likely occurs because these products ________.

  1. inhibits ADH release
  2. stimulates ADH release
  3. inhibits TSH release
  4. stimulates TSH release

FSH and LH release from the anterior pituitary is stimulated by ________.

What hormone is produced by beta cells of the pancreas?

When blood calcium levels are low, PTH stimulates ________.

  1. excretion of calcium from the kidneys
  2. excretion of calcium from the intestines
  3. osteoblasts
  4. osteoclasts
  1. inhibits antidiuretic hormone release
  2. stimulates antidiuretic hormone release
  3. inhibits parathyroid hormone release
  4. stimulates parathyroid hormone release
  1. follicle-stimulating hormone
  2. luteinizing hormone
  3. inhibin
  4. gonadotropin-releasing hormone
  1. Her uterus will not contract during childbirth.
  2. She will not ovulate.
  3. Her body will not be prepared for pregnancy.
  4. She will be unable to produce milk.
  1. excretion of calcium from the kidneys
  2. excretion of calcium from the intestines
  3. osteoblasts
  4. osteoclasts
  1. symmetric body formation
  2. excessive body growth
  3. enlarged hand, feet, and face bones
  4. weak bones and nervous system impairment
  1. Hormone release is stimulated by the nervous system.
  2. Hormone release is stimulated by change in the blood.
  3. Hormone release is stimulated by the external environment.
  4. Hormone release is stimulated by another hormone.
  1. TSH production is triggered by the nervous system.
  2. TSH production is triggered by blood ion concentration change.
  3. TSH triggers epinephrine production.
  4. TSH triggers the production of T3 and T4.
  1. humoral stimulus
  2. hormonal stimulus
  3. neural stimulus
  4. negative stimulus
  1. regulate circadian rhythms
  2. regulate secondary sex characteristics
  3. regulate blood calcium levels
  4. regulate blood glucose
  1. The adrenal cortex produces renin, which affects aldosterone secretion by the kidneys.
  2. The kidneys produce renin, which affects aldosterone secretion by the adrenal cortex.
  3. The kidneys produce calcitriol, which affects renin secretion by the adrenal cortex.
  4. The kidneys produce calcitriol, which affects aldosterone secretion by the adrenal cortex.

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    Auxin Receptors and Plant Development: A New Signaling Paradigm

    The plant hormone auxin, in particular indole-3-acetic acid (IAA), is a key regulator of virtually every aspect of plant growth and development. Auxin regulates transcription by rapidly modulating levels of Aux/IAA proteins throughout development. Recent studies demonstrate that auxin perception occurs through a novel mechanism. Auxin binds to TIR1, the F-box subunit of the ubiquitin ligase complex SCF TIR1 , and stabilizes the interaction between TIR1 and Aux/IAA substrates. This interaction results in Aux/IAA ubiquitination and subsequent degradation. Regulation of the Aux/IAA protein family by TIR1 and TIR1-like auxin receptors (AFBs) links auxin action to transcriptional regulation and provides a model by which the vast array of auxin influences on development may be understood. Moreover, auxin receptor function is the first example of small-molecule regulation of an SCF ubiquitin ligase and may have important implications for studies of regulated protein degradation in other species, including animals.


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