negative regulation of growth hormone secretion

Definition

Target type: biologicalprocess

Any process that decreases or stops the frequency, rate or extent of the regulated release of growth hormone from a cell. [GOC:dph]

Negative regulation of growth hormone secretion is a complex process that involves multiple regulatory pathways and feedback loops. It ensures that growth hormone (GH) production and release are tightly controlled, preventing excessive growth and maintaining overall homeostasis.

**Hypothalamic-Pituitary Axis:**
The primary regulatory mechanism for GH secretion involves the hypothalamic-pituitary axis. The hypothalamus, located in the brain, produces two key hormones that regulate GH release from the pituitary gland:
- **Growth hormone-releasing hormone (GHRH):** Stimulates GH synthesis and release from the anterior pituitary gland.
- **Somatostatin:** Inhibits GH release from the anterior pituitary gland.

**Feedback Mechanisms:**
- **Negative feedback by GH:** GH itself acts as a negative regulator, inhibiting the release of GHRH from the hypothalamus and suppressing its own production by the pituitary gland. This feedback loop helps maintain appropriate GH levels.
- **Negative feedback by insulin-like growth factor 1 (IGF-1):** IGF-1, a hormone produced in response to GH action, also exerts negative feedback. IGF-1 directly inhibits GH release from the pituitary and indirectly suppresses GHRH secretion from the hypothalamus.

**Other Regulatory Factors:**
- **Stress:** Psychological and physical stress can suppress GH secretion.
- **Nutritional status:** Malnutrition or fasting can decrease GH production.
- **Sleep:** Deep sleep stages promote GH release, while sleep deprivation can reduce it.
- **Age:** GH secretion naturally declines with age.
- **Hormones:** Other hormones, including thyroid hormones, cortisol, and sex hormones, can influence GH regulation.

**Molecular Mechanisms:**
The negative regulation of GH secretion involves various molecular mechanisms, including:
- **G protein-coupled receptor signaling:** GHRH and somatostatin bind to their respective G protein-coupled receptors on pituitary cells, triggering intracellular signaling cascades that regulate GH production and release.
- **Gene expression regulation:** Transcription factors and signaling pathways influence the expression of genes involved in GH synthesis and release.
- **Post-translational modifications:** GH undergoes post-translational modifications, such as phosphorylation, that can affect its stability and secretion.

**Consequences of Dysregulation:**
Disruption of negative regulation of GH secretion can lead to various clinical conditions, including:
- **Gigantism:** Excessive GH production during childhood can result in abnormally tall stature.
- **Acromegaly:** Excessive GH production in adulthood can cause thickening of bones and soft tissues.
- **Dwarfism:** Insufficient GH production during childhood can lead to short stature.

**Conclusion:**
Negative regulation of growth hormone secretion is a complex and tightly controlled process that ensures appropriate GH levels throughout life. It involves multiple regulatory pathways and feedback loops, ensuring proper growth and overall homeostasis.'
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Compounds (24)