Gonadotropin hormones and their receptors

LH and FSH

-are secreted by very specific kinds of cells in the anterior pituitary called the basophils -approximately 10-20% of the molecular structure of LH and FSH are carbohydrates and they are more specifically known as glycoproteins. -Each glycoprotein has 2 subunits: alpha and beta -these subunits have no biological activity separately; both subunits are necessary to produce a biological response -alpha subunits between LH and FSH are identical, its the beta subunits that makes them different from one another and allow for their unique biological function. -LH and FSH are gonadotropins because in response to GnRH (from hypothalamus) they stimulate steroidogenesis in the gonads as well as the development and maturation of the gametes.

After a peptide hormone delivers its message to a target cell, the signal must end

-groups of ligand-bound cell surface receptors pinch off as a small vesicle and are internalized into the cell. In the cytoplasm, the ligand-receptor complex is degraded. -the hormone is degraded and the receptor may be recycled back to the cell surface.

General features of protein hormones

-tend to be larger molecules -more fragile: break up within seconds -water soluble: action is much shorter -receptors: found in cell membrane

2 functional classes of receptors

1) Enzymatic: -Cytoplasmic domain: enzymes -activation of other enzymes Result: changes in cellular functioning 2) 2nd messenger activities: Coupled with G proteins a) Activation of intracellular enzyme, formation of cAMP (2nd messenger) b) Signal transduction pathways that don't rely on cAMP Result: changes in cellular functioning

Signal amplification by 2nd messengers

1) G proteins comprise of 3 different subunits which often dissociate after the protein receptor is occupied by its hormonal ligand. 2) Alpha subunit may interact with an effector protein (ion channel or an enzyme) to open various channels or activate various protein kinases. 3) Beta and gamma subunits form a complex that binds to a protein kinase that may feed back to influence the hormone receptor.

IP3/DAG signal transduction

1) Inositol triphosphate and diacylglycerol signal transduction begins with the binding of a hormone to the extracellular domain of a G protein-coupled receptor. 2) The alpha-subunit of the activated G protein activates phosphorlipase C (PLC) which evokes the hydrolysis of PIP2 and subsequent formation of IP3 and DAG 3) IP3 mobilizes calcium calcium from stores in endoplasmic reticulum and possibly moves calcium into the cell. 2 ways to mobilize calcium; one is to release it from its stores in the endoplasmic reticulum and the other is to bring the calcium inside the cell. 4) It is a twin signal, DAG also assists with rise in calcium concentrations and evokes PKC (protein kinase C) binding to the cell membrane and further activation of calcium channels.

Protein and peptide hormone receptors

1) Peptide or protein hormone binds to its receptor 2) cytoplasmic tyrosine kinase domain changes its shape -tyrosine kinase is an enzyme which that catalyzes the transfer of a phosphate group from ATP to a protein kinase. 3) This conformational change allows the receptor to interact with an intracellular protein kinase and ATP 4) phosphorylation activates the protein kinase, which can now activate other substrates within the cell and causes specific changes in cellular function. 5) after enzymatic degradation of the bound hormone, the receptor releases its ligand and returns to its unoccupied state and conformation.

Functions of hypothalamus

1) release of major hormones 2) thermoregulation 3) control of food and water intake 4) sexual behaviour and reproduction 5) daily cycles in physiological state 6) mediation of emotional responses

Hypothalamus

A neural structure lying below the thalamus; it directs several maintenance activities (eating, drinking, body temperature), helps govern the endocrine system via the pituitary gland, and is linked to emotion and reward. -made up of a lot of different nuclei Nuclei: refers to a cluster of neurons in an area that are engaged in similar activities.

What are gonadotropins?

FSH and LH -hormones that are secreted from the pituitary gland in the brain and they act on the gonads (ovaries and testes)

G protein receptors (work with g protein)

G protein: 3 subunits

Glycoprotein hormones

LH, FSH, TSH, hCG -tend to be larger molecules -non-covalently bound -common alpha subunit but different beta subunit (beta subunits have more amino acid residues)

Sphenoid bone

Lies at base of the skull, in the bone there is a small cup called "sella turcica", the pituitary gland or (hypophysis) lies in the cup. -sphenoid bone lies at the base of the skull, and in this bone is a small-cup shaped depression Lying in this depression is a round ball of tissue, about 1.3 cm in diameter, called the pituitary gland (hypophysis)

Tuberal (middle) region

Nuclei: Arcuate Hormones: GnRH

Supraoptic or anterior region of the hypothalamus

Nuclei: supraoptic and paraventricular Hormones: oxytocin and corticotropin-releasing hormone (CRH)

Importance of the Hypothalamus

Often called the pharmacological museum, not only is it producing neurohormones but also neurotransmitters. List include: ACh, GABA, glutamate, serotonin, dopamine dozen of peptides have been identified in recent years

Protein hormones that are only a few amino acids in length

Peptide hormones

Protein hormones with many amino acids in length

Polypeptide hormones or protein hormones

Protein hormone receptors

are called transmembrane receptors and are found embedded in the phospholipid bilayer of the cell membrane. 3 domains: 1) extracellular binding domain to which the peptide or protein hormone binds (extracellular) 2) complex transmembrane domain that may be small or large (transmembrane) 3) cytoplasmic domain inside the cell (intracellular)

Diencephalon

contains the thalamus, hypothalamus, and epithalamus

Extracellular domain

has a ligand-binding area -ligand is what attaches to binding area (hormone in our case) -Hormone is also referred to as first messenger (generic name) -first chemical that result in cascade of events that occur when binding happens.

Protein hormones include

neurohormones of hypothalamus, tropic hormones of the anterior pituitary, and posterior pituitary hormones Tropic: class of hormones from anterior pituitary that affect secretions of hormones from other endocrine glands. Protein and peptide hormones are produced in endocrine cells and are released into the circulatory system via exocytosis.

Protein Hormones

released from hypothalamus & pituitary gland -most vertebrate hormones are protein hormones

Thalamus

the brain's sensory switchboard, located on top of the brainstem; it directs messages to the sensory receiving areas in the cortex and transmits replies to the cerebellum and medulla -takes all the information gathered from our sensory system and then passes it onto different parts of the brain.