Pituitary Gland and Hormones

Overview of Pituitary Gland Functions and Structure

Hormones Secreted by the Pituitary Gland

The pituitary gland secretes hormones critical for controlling various bodily functions:

  • Uterine contractility

  • Milk production and secretion

  • Water balance

  • Blood pressure regulation

  • Reproductive function

  • Growth stimulation

  • Metabolic processes

  • Osmoregulation

Regulation of Pituitary Function

The function of the pituitary gland is regulated by neurohormones produced in the hypothalamus. Specific clusters of neurons in the hypothalamus known as hypothalamic nuclei play a crucial role in this regulatory process, which includes:

  • Supraoptic nuclei

    • ADH

    • water balance blood pressure

    • axons to the posterior pituitary

  • Paraventricular nuclei

    • some ADH production

    • oxytocin production-milk production, uterine contraction

    • oxytocin is stored and released by the axons of the posterior pituitary

    • CRH (corticotropin-releasing hormone) which regulates ACTH release from anterior pituitary and worths with stress appetite and autonomic control

    • CRH works through the portal

  • Preoptic nuclei

    • thermoregulation

    • gnRH neurons which release into portal system

    • sexually diamorphic behaviours

Structural Anatomy of the Pituitary Gland (Hypophysis)

Embryological Origin

The pituitary gland, also known as the hypophysis, has distinct embryological origins:

  • Anterior pituitary: Derives from an outgrowth of the dorsal buccal cavity (roof of the mouth).

  • Posterior pituitary: Develops from the brain.

  • Intermediate lobe: Located between the anterior and posterior pituitary, associated with the adenohypophysis, which may not be present in some species like certain mammals, birds, hagfish, and lampreys.

Anatomy of Adenohypophysis

  • Pars tuberalis (tuberal lobe)

  • Pars intermedia (intermediate lobe)

  • Pars distalis (anterior lobe)

Anatomy of Neurohypophysis

  • Infundibulum (neural lobe)

  • Pars nervosa (specific region within the posterior pituitary)

Hormones of the Posterior Pituitary (Neurohypophysis)

  1. Vasopressin (AVP, also known as Arginine vasopressin; with Arg at position 8): Contains a sequence of 9 amino acids.

    • Structure: Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly-NH2

  2. Oxytocin: Another peptide hormone also composed of 9 amino acids.

    • Structure: Cys-Tyr-Ileu-Gln-Asn-Cys-Pro-Leu-Gly-NH2

Other Hormones

In addition to the primary vasopressin and oxytocin, there are structurally different neurohypophysial hormones found within mammalian and non-mammalian vertebrates.

Synthesis of Vasopressin (ADH) and Oxytocin

Vasopressin and oxytocin are synthesized in the cell bodies of neurons located within the supraoptic and paraventricular nuclei of the hypothalamus. These hormones are then transported to the terminals located in the posterior pituitary, where they are released into circulation.

Actions of Vasopressin (AVP)

Vasopressin acts through two types of membrane receptors:

  • V1 receptors: Mediate vascular smooth muscle contraction leading to increased blood pressure.

  • V2 receptors: Responsible for the renal actions of vasopressin, facilitating water reabsorption.

Memory Effects of Vasopressin

Vasopressin has been shown to facilitate memory consolidation, with studies indicating that AVP treatment improves short-term memory in aged humans.

Blood Pressure Regulation by Vasopressin

  • Decreased blood pressure: Activates baroreceptors leading to increased AVP secretion, which promotes water uptake (via V2 receptors) and constriction of arterioles (via V1 receptors), culminating in increased blood pressure. Control Data for AVP Release:

    • A decline in arterial blood pressure is positively correlated with increased levels of plasma AVP (depicted on a graph).

Osmolality Regulation by Vasopressin

  • Increased blood osmolality (reflected by rising sodium concentration [Na+]): Activates osmoreceptors in the central nervous system, resulting in increased AVP secretion, which leads to:

    • Water retention (via V2)

    • Increased sodium secretion (also via V2)

    • Concentration of urine and reduction of urine volume

The response of AVP to changes in plasma osmolality is notably sensitive, with release being activated by as little as a 1% change.

Summary of AVP Release Regulation

Factors stimulating and inhibiting AVP release include:

  • Stimulation:

    • Extracellular fluid (ECF) osmolality

    • Body temperature

    • Blood volume

    • Blood pressure

    • Stress

    • pain

    • Na+ on CSF

    • nicotines, opiates, barbiturates

  • Inhibition:

    • Ethanol

    • low temperature

Oxytocin and Milk Release

Oxytocin is critically involved in the control of milk release after parturition (birth).

  • Suckling activates sensory nerves in the areolae and nipples, stimulating the secretion of oxytocin.

  • Oxytocin induces milk ejection by contracting the myoepithelial cells of the mammary gland.

Uterine Contraction and Parturition

  • Oxytocin stimulates contractions of the myometrium (uterine muscle), facilitating labor. Over time, as the fetus enters the birth canal, the cervix and vagina become stretched, enhancing the secretion of oxytocin and thereby producing stronger uterine contractions.

  • This positive feedback loop further aids in the descent of the fetus during birth.

Anterior Lobe of the Pituitary Gland

The anterior lobe contains a variety of cell types that secrete various hormones:

  • Gonadotropes: Secrete Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH)

  • Lactotropes: Secrete Prolactin (PRL)

  • Somatotropes: Secrete Growth Hormone (GH)

  • Corticotropes: Secrete Adrenocorticotropic Hormone (ACTH)

  • Thyrotropes: Secrete Thyroid-Stimulating Hormone (TSH)

Hormonal Families of the Adenohypophysis

At least three different families of peptide hormones originate from the adenohypophysis:

  1. Family I: Growth Hormone (GH) and Prolactin (PRL)

  2. Family II: Glycoprotein hormones, including thyroid-stimulating hormone (TSH) and gonadotropins (FSH, LH)

  3. Family III: Hormones derived from Pro-opiomelanocortin (POMC)

Family I Hormones

  1. Growth Hormone (GH) and Prolactin (PRL): Both consist of approximately 200 amino acids, forming a single-chain protein structure.

Family II Hormones - Glycoprotein Hormones

Include:

  • Thyroid Stimulating Hormone (TSH)

  • Gonadotropin Hormones:

    • Follicle-Stimulating Hormone (FSH)

    • Luteinizing Hormone (LH)

    • Chorionic Gonadotropin: Secreted by the placenta during pregnancy.

Structure

Glycoprotein hormones comprise two subunits, alpha and beta, which are non-covalently linked. The separate subunits are inactive. The alpha subunit is identical across all glycoprotein hormones, while beta subunits are unique, conferring specific biological activity.

Family III Hormones - Derived from Pro-opiomelanocortin (POMC)

POMC precursors give rise to:

  • Adrenocorticotropic Hormone (ACTH)

  • Melanocyte-Stimulating Hormone (α-MSH, β-MSH)

  • β-Endorphin

  • β-Lipotropic Hormone (β-LPH)

Cleavage Mechanism

POMC is expressed in various cell types where the derived peptides (ACTH, MSH, β-Endorphin, β-LPH) are specifically cleaved by a family of prohormone convertases, with the expression varying by cell type.

α-Melanocyte-Stimulating Hormone (MSH)

  • The precursor protein, POMC, encodes α-MSH, a 13 amino acid peptide that is secreted from melanotropes in the pars intermedia (often absent in adult humans, birds, and certain aquatic mammals).

  • The size of the pars intermedia correlates with the ability of an animal to change color.

  • Action: α-MSH stimulates melanin dispersal in melanocytes, resulting in skin darkening.

Prolactin: Functions and Regulation

  • Prolactin is a versatile hormone with a broad range of effects across various species.

Factors Influencing Prolactin Release

  • Dopamine (DA): Strong inhibitor of prolactin release.

  • Cholecystokinin (CCK): Weak stimulator of prolactin release.

Reproductive Actions of Prolactin

In males:

  • Increases and maintains LH receptors in testes to sustain testosterone levels.

  • Enhances sperm motility.

In females:

  • Stimulates lactation by promoting synthesis of casein and fatty acids.

  • Increases progesterone synthesis and facilitates migration of IgA lymphoblasts to mammary glands.

  • Plays a role in osmoregulation within the uterus.

  • High prolactin levels observed during lactation reduce gonadotropin production, suppressing sexual activity.

Growth Hormone (GH) Regulation and Effects

Control of GH Secretion

GH release is influenced by:

  • Growth Hormone-Releasing Hormone (GHRH) (44 amino acids)

  • Somatostatin (~28 amino acids)

Inducing Factors for GH Release

  • IGF-I

  • Hypoglycemia (low blood sugar)

  • High-protein meals

  • Fatty acids

Mechanism of Action

GH functions by stimulating somatic growth in skeletal and soft tissues. Its effects are direct at the target cells and also occur indirectly via growth factors such as IGF-I and IGF-II.
IGF 2 is not dependent on GH and important for fetal development

Physiological Actions of GH

  • Increases blood sugar levels by reducing glucose oxidation and suppressing glucose uptake in muscles.

  • Works alongside thyroid hormones and cortisol to regulate growth.

GH Deficiency and Excess

  • GH Deficiency: Early deficits lead to dwarfism; in adults, symptoms include weakness and changes in skin appearance. Treatment includes GH replacement therapy.
    Laron syndrome- GH resistance, receptor issuesmall head, prominent forhead, underdeveloped jaw, normal inteligence

  • treatment for landons is recombinant IGF-1 therapy

  • GH Excess: Leads to gigantism if it occurs before epiphyseal closure, resulting in disproportionately long limbs; or acromegaly (enlargement of the skull, jaw, and soft tissue) if it occurs after growth cessation. Treatment options include tumor removal or administration of somatostatin analogs.

Thyroid Stimulating Hormone (TSH)

Structural Components

  • TSH is a glycoprotein hormone composed of two subunits: alpha and beta.

    • Alpha subunit: Contains 89 amino acids.

    • Beta subunit: Contains 112 amino acids.

Functions of TSH

  • Stimulates synthesis of thyroglobulin (Tg) and thyroid hormones (T3 and T4).

  • Chronic elevation of TSH levels can lead to hypertrophy (increased cell size) and hyperplasia (increased cell number) of thyroid follicles.

Goiter Formation

  • Goiter Development: Characterized by low levels of T3 and T4 alongside high TSH levels, often resulting from iodine deficiency:

    Decreased synthesis of T3 and T4 → Increased TSH → Enlargement (hyperplasia) of the gland.

Synthesis of Thyroid Hormones

The synthesis process consists of four key steps:

  1. Iodide trapping

  2. Oxidation of iodide (I-) to iodine (I2)

  3. Iodination of tyrosyl residues

  4. Oxidative coupling of iodinated tyrosines to form T4 and T3, which are stored in the colloid space.

Functionality of T3 and T4

  • T4, although the principal product of the thyroid gland, is converted to the active hormone T3 outside the thyroid in various tissues, including the liver and kidneys.

Physiological Effects of Thyroid Hormones

  1. Metamorphosis: Thyroid hormones stimulate metamorphosis in amphibian larvae; thyroidectomized organisms remain in larval form, whereas administration of thyroid hormones can reverse this effect.

  2. Growth Effects: Thyroidectomy (removal of the thyroid gland) leads to stunted growth in birds and mammals; in newborn rats, this can cause malformations and delays in bone ossification, correctable with hormone therapy if administered early.

  3. Dental Eruption: Thyroid hormones influence the growth and eruption of teeth, with hypothyroid children experiencing significant delays in the arrival of permanent teeth.

  4. Nervous System Development: Thyroid hormones are crucial for brain development; thyroidectomy or anti-thyroid treatment in young rats results in smaller brains and fewer cortical axons.

Congenital Hypothyroidism

If not treated, this condition can lead to significant cognitive impairments.

  • Treatment: Thyroid hormone replacement can restore normal IQ levels if initiated within 6 weeks; delayed treatment typically results in lower IQ outcomes.

Thyroid Hormones and Metabolism

  • In birds and mammals, thyroid hormones are essential for maintaining basal metabolic rates; they increase oxygen consumption and heat production (calorigenesis).

  • In response to cold stimuli, hypothalamic TRH (Thyrotropin-releasing hormone) production increases, leading to elevated TSH and consequently increased production of thyroid hormones (T4 and T3), culminating in thermogenesis.

Additional Metabolic Functions

  • At physiological concentrations, thyroid hormones enhance protein synthesis, promote growth rates, and favor positive nitrogen balance as well as lipolysis, increasing free fatty acid levels in the bloodstream.