GH2 - Growth hormone 2 | Elisa - Clia - Antibody - Protein

Background

GH2 (Growth Hormone 2), also known as placental growth hormone, is a hormone closely related to GH1, the classical pituitary growth hormone. Unlike GH1, GH2 is primarily expressed in the placenta and plays a vital role in modulating maternal metabolism during pregnancy to support fetal growth. GH2 is part of the growth hormone/chorionic somatomammotropin (GH/CSH) gene cluster located on chromosome 17, which includes genes for both growth hormones and placental lactogens. GH2 exhibits significant sequence homology with GH1 but differs in its expression pattern and physiological functions. It replaces GH1 in the maternal circulation during pregnancy, altering nutrient availability and metabolism to ensure adequate support for the developing fetus.

Protein Structure

GH2 is a polypeptide hormone comprising 191 amino acids, with a molecular weight of approximately 22 kDa. Its structure is similar to other members of the growth hormone family and includes:

1. Four-Helix Bundle: The protein consists of a characteristic four α-helix bundle, which is stabilized by two intramolecular disulfide bonds.
2. Receptor-Binding Sites: GH2 interacts with the growth hormone receptor (GHR) via two binding sites, facilitating its signaling functions.
3. Post-Translational Modifications: Glycosylation and cleavage contribute to its functional diversity and stability in circulation.
4. Homology with GH1: GH2 shares 85-90% amino acid identity with GH1 but has slight variations that influence its receptor affinity and functional specificity.

GH2's structural features are critical for its binding to GHR and subsequent activation of downstream signaling pathways.

Classification and Subtypes

GH2 is a member of the growth hormone/prolactin family, which includes:

1. Growth Hormones: GH1 (pituitary growth hormone) and GH2 (placental growth hormone).
2. Chorionic Somatomammotropins: Also known as placental lactogens, which are involved in lactation and metabolic regulation during pregnancy.

Unlike GH1, GH2 is expressed exclusively in the placenta, where it gradually replaces pituitary GH in the maternal circulation during the second half of pregnancy.

Function and Biological Significance

GH2 has both growth-promoting and metabolic functions, many of which are unique to pregnancy:

1. Maternal Metabolism: GH2 enhances maternal insulin resistance, ensuring a consistent supply of glucose and amino acids to the fetus.
2. Fetal Growth: By modulating nutrient availability and promoting lipolysis, GH2 supports fetal development and growth.
3. Placental Function: GH2 plays a role in maintaining placental health and may regulate placental cell proliferation and differentiation.
4. Growth Hormone Receptor Activation: GH2 binds to GHR, activating signaling pathways such as the JAK-STAT, PI3K-Akt, and MAPK pathways, which are involved in growth and metabolism.
5. Immune Modulation: GH2 has potential roles in modulating maternal immune responses, creating a favorable environment for the fetus.

GH2’s activity is crucial for orchestrating the metabolic changes required during pregnancy to support both maternal and fetal health.

Clinical Issues

Abnormal GH2 expression or activity is associated with various pregnancy-related and developmental disorders:

1. Intrauterine Growth Restriction (IUGR): Dysregulated GH2 levels can impair fetal growth by altering nutrient availability.
2. Gestational Diabetes Mellitus (GDM): Excessive GH2-induced insulin resistance can contribute to the development of gestational diabetes.
3. Placental Dysfunction: Aberrant GH2 expression is linked to placental insufficiency and associated complications, such as preeclampsia.
4. Growth Disorders: Although GH2 primarily acts during pregnancy, variations in its function may have downstream effects on postnatal growth and development.
5. Cancer: GH2’s ability to stimulate growth pathways raises questions about its potential involvement in promoting cell proliferation in certain cancers, though this remains an area of ongoing research.

Summary

GH2, or placental growth hormone, is a crucial hormone expressed in the placenta that regulates maternal metabolism to support fetal growth. Structurally similar to GH1, GH2 facilitates nutrient supply and energy balance through its interaction with the growth hormone receptor and activation of downstream signaling pathways. Dysregulation of GH2 is implicated in pregnancy-related complications such as IUGR and GDM. Understanding GH2’s unique functions and mechanisms offers insights into maternal-fetal health and potential therapeutic strategies for managing pregnancy-related disorders.