Endocrinology: Hormones, Receptors, and Signal Transduction

What is endocrinology?

The study of hormones.

What is a hormone?

A substance secreted directly into the blood by specialised cells.

How are hormones present in the blood?

In minute concentrations and bind specific receptors in target cells to influence cellular reactions.

Name the major endocrine glands.

Hypothalamus, Pituitary, Thyroid, Parathyroids, Adrenals, Pancreas, Ovary, Testes.

What are some endocrine organs?

Heart, Liver, Intestines, Kidney, Skin.

List some actions of hormones.

Fetal development, Cell growth, Metabolism, Cardiovascular function, Renal function, Skeletal function, Reproductive function, Immune function, Central nervous system function.

How can hormones affect behavior?

Examples include pre-menstrual tension, pregnancy-related depression, effects of high dose steroids, hypogonadism, and insulinoma.

What is the primary function of the endocrine system?

To maintain homeostasis.

What type of feedback mechanisms does the endocrine system use?

Usually negative feedback.

What are the characteristics of hormones?

Hormones are signaling molecules that can be steroids, amino acid derivatives, or peptides.

What are peptide hormones?

Hormones that range from 10-20 amino acids to hundreds of amino acids in size and are water soluble.

How are peptide hormones stored?

They can be stored in vesicles and released by exocytosis in response to a signal.

Describe the synthesis and release of polypeptide hormones.

mRNA binds amino acids into a preprohormone, which is processed into an inactive prohormone and then into active peptides in secretory vesicles.

What are prohormones?

Protein hormone precursors that require additional enzymes for activation.

What are amino acid derivatives?

Hormones synthesized from amino acids, such as thyroid hormones from tyrosine.

What is the process of synthesizing thyroid hormones?

Thyroglobulin is synthesized, iodide is trapped and oxidized, and iodinated tyrosines are linked to form T3 and T4.

What are steroid hormones?

Hormones that are lipophilic and easily pass through the plasma membrane, made from cholesterol.

How are steroid hormones synthesized?

They are produced on demand from cholesterol and are not stored.

What are the three types of steroid hormones?

Mineralocorticoids, Glucocorticoids, Androgens.

What is the rate-limiting step in steroid hormone synthesis?

The transport of cholesterol into mitochondria, which is StAR-dependent.

What is the role of StAR in steroid hormone synthesis?

StAR is an enzyme induced by ACTH that transports cholesterol into mitochondria.

What is the function of hormone receptors?

Hormones alter protein function or gene transcription through their receptors.

What is a hormone receptor?

A protein on or inside a cell that binds to a specific hormone.

What are the key characteristics of hormone receptors?

They must bind the hormone specifically, detect it among other molecules, have high affinity, be present in specific tissues, be saturable, and bind in a reversible manner.

What are the two main types of hormone receptors?

Cell surface receptors and intracellular receptors.

What is the function of Tyrosine Kinase?

An enzyme that transfers a phosphate group from ATP to a tyrosine residue in a protein, inducing conformational changes.

What are the two types of Tyrosine Kinase activity?

Intrinsic and recruited.

Give an example of an intrinsic Tyrosine Kinase activity.

Epidermal growth factor receptor (EGF receptor) or insulin receptor.

What is the role of EGF as an extracellular receptor?

It induces ligand-induced dimerization and is involved in autocrine and paracrine cell signaling.

What are the key components of the EGF receptor (EGFR)?

A hormone binding site, two cysteine-rich regions, a single trans-membrane region, and a kinase domain.

What is the basic mechanism of receptor modification?

Involves post-translational modification with forward reactions by kinases and reverse reactions by phosphatases.

What activates RAS?

RAS is activated by GTP.

What is the function of G Protein Coupled Receptors (GPCRs)?

They act via second messenger molecules to transfer signals into the cell.

Name some second messengers involved in GPCR signaling.

Cyclic AMP (cAMP), inositol 1,4,5-triphosphate (IP3), diacylglycerol (DAG).

What are the subunits of G Proteins?

G Proteins are heterotrimeric, consisting of α, β, and γ subunits.

What happens when a GPCR is activated?

The α subunit exchanges GDP for GTP and is released to activate second messengers.

What is the role of diacylglycerol (DAG) and Ca2+ in signaling?

DAG and Ca2+ are involved in the production of phosphorylated proteins or modified substrates.

What is the summary of peptide hormone receptors?

They bind to a cell surface receptor linked to Tyrosine Kinase or G protein coupled receptors, with the hormone as the 1st messenger and 2nd messengers facilitating intracellular signaling.

What characterizes steroid hormone receptors?

They are small lipophilic molecules that bind to DNA and function as transcription factors.

What are Type 1 nuclear hormone receptors?

Receptors for glucocorticoids, mineralocorticoids, progesterone, estrogen, and androgen that form dimers and bind to hormone response elements (HREs).

What happens upon ligand binding to Type 1 nuclear receptors?

Heat shock proteins dissociate, leading to homo-dimerization, translocation to the nucleus, and binding to DNA.

What are Type 2 nuclear hormone receptors?

Receptors that heterodimerize with RXR and are retained in the nucleus, binding to DNA regardless of ligand status.

What occurs when a ligand binds to Type 2 nuclear receptors?

Dissociation of co-repressor proteins and recruitment of co-activator proteins, leading to transcription of DNA into mRNA.

What is the role of the nuclear receptor superfamily?

They are proteins with conserved structures that function as transcription factors.

How do hormones alter gene expression?

By binding to their receptors and interacting with target sequences of DNA, specifically at hormone response elements (HREs).

What is a promoter in the context of gene expression?

The region of DNA where RNA polymerase attaches and initiates transcription.

What is the structure of Hormone Response Elements (HREs)?

Usually consist of a 6 bp hexamer core recognition motif with two half-sites and intervening base pairs.

What is the function of the first and second zinc finger domains in HRE recognition?

The first zinc finger domain binds DNA, while the second is involved in dimensional recognition.

What is the function of the P-box in nuclear receptors?

The P-box contains zinc fingers and recognition sequences for hormones.

What are nuclear receptors?

Cytoplasmic or nuclear ligand-dependent transcription factors with a constitutive transactivation domain and a centrally conserved DNA binding domain.

What is the role of the hypothalamus?

It controls autonomic and endocrine functions, important for homeostasis and primitive functions.

How does the hypothalamus respond to environmental factors?

It responds to light (circadian rhythm), stress, neural signals, visceral afferents, and hormones.

What are the two lobes of the pituitary gland?

Anterior (adenohypophysis) and posterior (neurohypophysis) lobes.

How are anterior pituitary hormones regulated?

They are regulated by secreted hypothalamic factors.

What hormones are synthesized in the posterior pituitary?

Posterior pituitary hormones are synthesized in the hypothalamus and transported via neuronal projections.

What are tropic hormones?

Hormones that target other endocrine glands.

Name the key hormones produced by the anterior pituitary.

Thyroid stimulating hormone (TSH), Follicle stimulating hormone (FSH), Luteinising hormone (LH), Adrenocorticotropic hormone (ACTH), Growth hormone, Prolactin.

What is the structure of thyroid stimulating hormone (TSH)?

TSH is a glycoprotein with a common α subunit and a unique β subunit.

What is the hypothalamic-pituitary-thyroid axis?

A regulatory pathway involving the hypothalamus, pituitary gland, and thyroid gland.

What is the function of gonadotrophins?

LH and FSH regulate testosterone biosynthesis and spermatogenesis in males, and the menstrual cycle and fertility in females.

What is the role of Adrenocorticotropic Hormone (ACTH)?

ACTH stimulates the conversion of cholesterol to cortisol or sex steroid precursors.

What is the source of ACTH?

ACTH is synthesized from Pro-opiomelanocortin (POMC) in corticotrophs of the anterior pituitary.

What effects does prolactin have?

Prolactin stimulates mammary gland development, DNA synthesis, epithelial cell proliferation, and maintains lactation.

What are prolactinomas?

The most common type of pituitary tumors that interfere with the HPG axis, causing infertility and galactorrhoea.

What regulates growth hormone release?

Factors include GHRH, dopamine, catecholamines, thyroid hormone, and somatostatin.

What is Laron syndrome?

A condition caused by GH receptor mutations leading to dwarfism, treated with IGF-1.

How does GH deficiency manifest?

GH deficiency can be treated with recombinant human growth hormone.

What is the significance of pulsatile secretion in hormone regulation?

Pulsatile secretion is essential for the actions of hormones like LH and FSH.

What is the role of glucocorticoids in relation to prolactin?

Glucocorticoids synergize with prolactin in stimulating mammary gland development.

What are the effects of stress on ACTH levels?

ACTH levels rise with stress, such as hypoglycaemia, which is used clinically to test corticotroph function.

What is the relationship between hypothyroidism and prolactin levels?

Hypothyroidism can lead to hyperprolactinaemia due to elevations in TRH.

What are the causes of hypopituitarism?

Pituitary tumor, brain surgery, trauma, radiotherapy, blocked blood supply, bleeding, inflammation, autoimmunity, and infection.

What is the function of TSH?

Stimulates growth of the gland and secretion of thyroid hormone.

What does FSH do in females?

Stimulates development of eggs and follicles in the ovaries.

What does FSH do in males?

Stimulates production of sperm in the testes.

What is the role of LH in females?

Stimulates ovulation and corpus luteum to secrete progesterone and estrogen.

What is the role of LH in males?

Stimulates interstitial cells of testes to secrete testosterone.

What does ACTH regulate?

Regulates response to stress and stimulates adrenal cortex to secrete corticosteroids.

What is the main effect of GH?

Stimulates liver to produce IGF-1.

What is the function of prolactin in females?

Stimulates milk synthesis after delivery.

What is the function of prolactin in males?

Increases LH sensitivity, leading to increased testosterone secretion.

What is Arginine Vasopressin (ADH)?

A nonapeptide secreted from the posterior pituitary that regulates water retention.

How does ADH affect plasma osmolarity?

Increases ADH to retain water when dehydrated, allowing reabsorption of free water from tubular fluid.

What happens during ADH excess?

Causes water retention, leading to low serum sodium concentration and highly concentrated urine (SIADH).

What happens during ADH deficiency?

Leads to excess water excretion, resulting in diabetes insipidus.

What are the symptoms of diabetes insipidus?

Polyuria (excess urine production) and polydipsia (excess drinking), with hypernatremia and increased serum osmolality.

What is the role of oxytocin?

Stimulates contraction of smooth muscle in the breast and uterus, involved in milk ejection reflex and parturition.

What hormones are secreted by the posterior pituitary gland?

ADH and oxytocin.

What hormones are produced by the adrenal cortex?

Corticosteroids, including glucocorticoids, mineralocorticoids, and androgens.

What is the rate-limiting step in steroid synthesis?

Transport of cholesterol into mitochondria, dependent on StAR protein.

What is StAR protein's function?

Transports cholesterol into mitochondria for steroidogenesis.

What enzyme converts cholesterol to pregnenolone?

Cytochrome P450scc (CYP11A).

What are glucocorticoids?

C21 steroids, including cortisol and corticosterone.

How is cortisol transported in the blood?

Over 90% bound to plasma proteins, primarily transcortin (CBG) and albumin.

What is ACTH's role in the adrenal gland?

Acts on the adrenal gland and can be cleaved into α-MSH and CLIP.

What is the function of α-MSH?

Regulates melanocytes.

What is the function of CLIP?

No known function.

What is the mechanism of action of glucocorticoids?

Glucocorticoids act through intracellular receptors (GR) and influence protein synthesis, e.g., lipocortin.

What are the systemic actions of glucocorticoids on metabolism?

They increase plasma glucose, enhance hepatic gluconeogenesis, inhibit glucose entry into tissues, and affect protein and fat metabolism.

How do glucocorticoids affect protein metabolism?

They increase protein breakdown in muscles, leading to amino acid release, and enhance protein synthesis in the liver.