Pituitary Gland: The Anterior Pituitary

Introduction

The anterior pituitary functions under precise hypothalamic control, coordinating multiple endocrine pathways. Growth hormone acts directly and via liver-derived mediators, while adrenocorticotropic hormone follows a circadian rhythm, highlighting the importance of neuroendocrine regulation in growth, metabolism, and daily physiological balance.

Pituitary Gland

• The pituitary gland is a central endocrine organ that regulates growth, reproduction, and metabolism throughout life. It influences childbirth, lactation, and developmental processes from infancy to adulthood.
• It helps maintain blood volume, arterial pressure, and stress responses.
• Pituitary dysfunction leads to significant multisystem clinical disorders.

Functional Anatomy

• The pituitary gland is located at the base of the brain within the sella turcica of the sphenoid bone.
• It consists of two distinct parts: anterior and posterior lobes, which differ in structure and function. The intermediate lobe is rudimentary in humans.
• The anterior lobe, called adenohypophysis, contains diverse endocrine cells that synthesize and secrete hormones.
• The posterior lobe, known as neurohypophysis, is composed of neural tissue and releases hormones produced in the hypothalamus.

Development

• The pituitary gland develops from two distinct embryological sources.
• The anterior lobe arises from Rathke’s pouch, an ectodermal outgrowth of the primitive oral cavity.
• The posterior lobe develops from neural tissue of the hypothalamus.
• The anterior lobe becomes glandular, forming the adenohypophysis.
• The posterior lobe differentiates into neuroendocrine tissue, forming the neurohypophysis.

Blood Supply

• The pituitary gland receives blood through superior and inferior hypophyseal arteries.
• The superior hypophyseal artery forms a primary capillary plexus in the median eminence.
• Long portal vessels arise from this plexus and descend to the anterior pituitary, forming a secondary capillary network. This arrangement constitutes the hypophyseal portal circulation, enabling direct transport of hypothalamic hormones.
• The inferior hypophyseal artery supplies the posterior pituitary.
• Short portal vessels may connect vascular networks within the gland.

Hormone Secretion

• The anterior pituitary contains fenestrated capillaries, allowing rapid exchange of substances.
• Endocrine cells store hormones in secretory granules.
• Hormones are released by exocytosis and enter the bloodstream immediately.

Anterior Pituitary

Hormones of Anterior Pituitary

• The anterior pituitary is a major endocrine gland that secretes hormones regulating growth, metabolism, and reproduction. It releases six principal hormones: growth hormone, thyroid stimulating hormone, adrenocorticotropic hormone, follicle stimulating hormone, luteinizing hormone, and prolactin.
• Additional peptides include beta lipotropin, melanocyte stimulating hormone, and certain cytokines.

Structure

• Most anterior pituitary hormones are polypeptides.
• Thyroid stimulating hormone, follicle stimulating hormone, and luteinizing hormone are glycoproteins composed of alpha and beta subunits. The alpha subunit is common, whereas the beta subunit determines hormonal specificity.

Control of Secretion and Major Effects

• Secretion is regulated by hypothalamic releasing and inhibiting hormones delivered through the portal circulation. These hormones control major endocrine glands such as thyroid, adrenal cortex, and gonads. They also influence growth, energy metabolism, and reproductive functions.
• Dysfunction produces widespread systemic effects due to hormonal imbalance.

Cell Types of Anterior Pituitary

Cells of the anterior pituitary are classified into chromophils and chromophobes.

Chromophil Cells

• Chromophils actively secrete hormones and are subdivided into acidophils and basophils.
• Acidophils include somatotrophs, which produce growth hormone, and lactotrophs, which produce prolactin.
• Basophils include corticotrophs, thyrotrophs, and gonadotrophs.
• Corticotrophs secrete adrenocorticotropic hormone and related peptides.
• Thyrotrophs release thyroid stimulating hormone.
• Gonadotrophs produce follicle stimulating hormone and luteinizing hormone.

Chromophobe Cells

Chromophobe cells are less active and contain fewer secretory granules.

Folliculostellate Cells

Folliculostellate cells are non endocrine cells that support pituitary function and release cytokines such as interleukin six.

Growth Hormone

• Growth hormone is secreted by somatotroph cells, which constitute nearly half of anterior pituitary endocrine cells.
• It promotes postnatal growth and is therefore called somatotropin.
• It does not significantly influence fetal growth.
• It maintains lean body mass, bone density, and metabolic balance in adults.

Structure

• Human growth hormone is a polypeptide consisting of 191 amino acids.
• It shows structural similarity with prolactin and placental lactogen.

Table 55.1: Hormone-secreting cells of the human anterior pituitary gland.

Cell Type	Proportion (%)	Staining	Hormone
Somatotrophs	40–50	Acidophilic	Growth hormone
Lactotrophs	10–25	Acidophilic	Prolactin
Corticotrophs	10–20	Basophilic	Adrenocorticotropic hormone
Thyrotrophs	3–5	Basophilic	Thyroid stimulating hormone
Gonadotrophs	10–15	Basophilic	Luteinizing and follicle stimulating hormones

Table 55.2: Factors affecting GH secretion.

Effect on GH Secretion	Key Factors
Increase	Hypoglycemia (fasting, exercise), high amino acid levels, estrogens, androgens, glucagon, stress, puberty, deep sleep, certain drugs, endogenous opioids
Decrease	Hyperglycemia, elevated free fatty acids, cortisol, growth hormone feedback, obesity, pregnancy, rapid eye movement sleep

Types, Secretion and Metabolism of GH

Growth hormone circulates mainly in two forms: 22 kilodalton variant (about 90 percent) and 20 kilodalton variant (about 10 percent).

Synthesis of GH

• It is synthesized as a prohormone in the rough endoplasmic reticulum of somatotroph cells.
• The precursor contains a signal peptide and a 191 amino acid hormone sequence.
• The signal peptide is removed during processing in the Golgi apparatus.
• The mature hormone is stored in secretory granules before release.
• Synthesis and secretion are regulated by hypothalamic hormones.
• Growth hormone releasing hormone stimulates gene expression and hormone production.
• Somatostatin inhibits synthesis and release of growth hormone.
• Thyroid hormones support normal growth hormone synthesis.
• Deficiency of thyroid function may reduce growth hormone production and impair growth.

Regulation of GH Secretion

• Growth hormone secretion is pulsatile and usually ranges from 0 to 5 nanograms per milliliter in adults. It is primarily regulated by the balance between growth hormone releasing hormone and somatostatin.
• Growth hormone releasing hormone stimulates, whereas somatostatin inhibits secretion from somatotroph cells.
• Growth hormone exerts feedback control on its own secretion. It suppresses growth hormone releasing hormone and enhances somatostatin release.
• It also stimulates formation of insulin like growth factor one in the liver. This factor further inhibits growth hormone secretion at both hypothalamic and pituitary levels.
• Ghrelin, produced mainly in the gastrointestinal tract, also stimulates growth hormone release.
• Various physiological factors influence secretion by modifying hypothalamic regulators.
• Exercise, stress, fasting, and protein rich meals enhance secretion.
• Growth hormone secretion varies across different life stages. It is elevated during infancy and remains adequate during childhood. A marked rise occurs at puberty, contributing to rapid growth and increased height. After puberty, secretion declines to adult levels and gradually reduces with aging.
• Secretion follows a circadian rhythm and occurs in bursts. The highest levels occur during deep sleep, particularly in the early part of the night. Approximately two thirds of daily secretion occurs during slow wave sleep. This pulsatile and regulated pattern ensures proper growth, metabolism, and tissue maintenance.

Metabolism

• Growth hormone circulates partly bound to a plasma growth hormone binding protein, derived from its receptor.
• About half of circulating hormone is protein bound, creating a transient reservoir in blood.
• The binding protein level reflects the density of growth hormone receptors in tissues.
• Growth hormone is cleared mainly by the liver through rapid metabolic degradation. Its biological half life is short, approximately 6 to 20 minutes.
• Basal plasma concentration in adults is usually below 3 nanograms per milliliter. ·  A small fraction is excreted unchanged in urine. Urinary excretion over 24 hours provides an indirect estimate of overall secretion.

Mechanisms of Action

• Growth hormone acts by binding to a specific membrane growth hormone receptor present on target cells. This receptor belongs to the cytokine receptor family and is associated with intracellular tyrosine kinase activity.
• The receptor has three structural regions: an extracellular binding domain, a transmembrane segment, and a cytoplasmic domain. It exists as two subunits, each capable of binding the hormone.
• Binding of growth hormone induces receptor dimerization, bringing the two subunits together. This structural change activates intracellular signaling pathways essential for hormone action.
• The primary pathway is the Janus kinase signal transducer and activator of transcription pathway.
• Activation of Janus kinase leads to phosphorylation of transcription factors. These factors enter the nucleus and regulate gene expression related to growth and metabolism.
• Another pathway involves SHC and growth factor receptor bound proteins, which activate mitogen activated protein kinase. This pathway promotes cellular growth and gene transcription.
• The insulin receptor substrate pathway is also stimulated, leading to activation of intracellular enzymes that regulate metabolism.
• Growth hormone signaling can also activate the phospholipase C pathway, generating intracellular messengers that increase calcium levels and influence cellular activity. These combined pathways mediate diverse effects such as protein synthesis, cell proliferation, and metabolic regulation.
• The coordinated activation of multiple signaling mechanisms ensures precise control of growth hormone actions in different tissues.

Physiological Actions of GH

• Growth hormone is an anabolic hormone with immediate metabolic and long term growth promoting effects. It directly stimulates lipolysis in adipose tissue and reduces glucose uptake in muscle. It increases hepatic gluconeogenesis, raising blood glucose levels. These actions shift energy use toward fat metabolism.

• Long term effects are mediated by insulin like growth factors, especially insulin like growth factor one. These factors promote cell division, tissue growth, and skeletal development.

Direct Actions of GH

Effects on Growth

• Growth hormone directly promotes linear growth by acting on the epiphyseal cartilage of long bones.
• It stimulates metabolic activity of chondrocytes, which are responsible for cartilage formation.
• It enhances incorporation of amino acids into collagen, improving structural matrix formation.
• It increases synthesis of proteoglycans such as chondroitin, contributing to cartilage strength.
• These components together form the extracellular matrix essential for bone elongation.
• Growth hormone increases amino acid uptake and accelerates protein synthesis in cartilage cells.
• It stimulates synthesis of ribonucleic acid and deoxyribonucleic acid, promoting cellular growth and division.
• It increases both the size and number of chondrocytes within growth plates. It also acts on precursor cells, promoting their differentiation into mature cartilage forming cells.
• These combined effects expand the epiphyseal cartilage, leading to longitudinal bone growth. ·  Linear growth continues until closure of epiphyseal plates, after which height increase ceases.

Other growth promoting effects of GH include:

• Growth hormone enhances skeletal growth by stimulating bone remodeling. It increases activity of osteoblasts and osteoclasts, with bone formation predominating. This results in increased bone mass and mineral content.
• In skeletal muscle, growth hormone promotes protein synthesis and cellular hypertrophy. It activates satellite cells, which contribute to muscle repair and growth. These effects improve muscle mass and functional capacity.
• Growth hormone stimulates enlargement of visceral organs such as liver, kidney, heart, pancreas, and intestine. It also influences growth of endocrine glands, skin, and connective tissue.
• Organ enlargement occurs through increased protein synthesis and enhanced ribonucleic acid and deoxyribonucleic acid synthesis. Both cell size and cell number increase, leading to hypertrophy and hyperplasia. These changes improve physiological functions such as digestion, cardiac output, and renal filtration.
• During puberty, growth hormone contributes to rapid increase in height. It enhances sensitivity of gonads to luteinizing hormone and follicle stimulating hormone. This supports sexual maturation and development of reproductive function.

Effects on Protein Metabolism

• Growth hormone promotes protein anabolism and supports overall somatic growth.
• It produces a positive nitrogen balance by enhancing protein synthesis.
• It increases amino acid uptake into cells across multiple tissues.
• It stimulates synthesis of ribonucleic acid and deoxyribonucleic acid, facilitating cellular growth.
• Plasma amino acid and urea levels decrease due to increased utilization for protein formation.

Effects on Carbohydrate Metabolism

• In carbohydrate metabolism, growth hormone has a diabetogenic effect.
• It increases hepatic glucose production through gluconeogenesis.
• It reduces glucose uptake in skeletal muscle, conserving glucose for essential organs.
• It decreases insulin sensitivity, contributing to elevated blood glucose levels.
• It indirectly enhances insulin secretion by increasing pancreatic responsiveness.
• Insulin like growth factor one exerts insulin-like actions and supports growth processes.

Effects on Fat Metabolism

• In fat metabolism, growth hormone stimulates lipolysis in adipose tissue.
• It increases circulating free fatty acids, which serve as an alternative energy source.
• Elevated fatty acids promote ketone body formation during fasting and stress.

Effects on Electrolyte and Water Metabolism

• Growth hormone also affects electrolyte and water balance.
• It increases calcium absorption from the intestine and enhances the action of vitamin D.
• It promotes sodium retention and reduces urinary loss of sodium and potassium.
• It helps maintain extracellular fluid volume through activation of hormonal systems regulating fluid balance.
• It increases phosphate reabsorption in renal tubules, raising plasma phosphate levels.
• These combined effects ensure adequate energy supply, tissue growth, and maintenance of internal balance.

Effects Mediated through IGFs

• Many growth promoting effects of growth hormone are mediated through insulin like growth factors. These factors were earlier termed somatomedins because they mediate somatic growth.
• The principal forms are insulin like growth factor one and insulin like growth factor two. They are polypeptides produced mainly in the liver, with additional synthesis in cartilage and other tissues. Their actions resemble insulin, particularly in promoting cellular growth and metabolism.

IGF-I

• Insulin like growth factor one is the dominant mediator of postnatal growth. It contains 70 amino acids and acts through receptors similar to insulin receptors. Its secretion is largely dependent on growth hormone after birth.
• Plasma levels increase during childhood, peak at puberty, and decline with aging.
• It circulates bound to binding proteins, especially insulin like growth factor binding protein three, which prolongs its action.
• It promotes cartilage formation, bone elongation, and protein synthesis.

IGF-II

• Insulin like growth factor two is relatively independent of growth hormone. It contains 67 amino acids and plays a major role in fetal growth and development.
• Its receptor is structurally distinct and related to mannose six phosphate receptors.
• In adults, its expression is limited to specific tissues such as meninges and choroid plexus.
• Plasma concentration remains relatively stable compared to insulin like growth factor one.
• Together, these growth factors ensure coordinated regulation of tissue growth, differentiation, and metabolic balance.

Applied Physiology

Hypersecretion of GH

• Hypersecretion of growth hormone produces distinct disorders depending on the timing of onset.
• Excess secretion before epiphyseal closure causes gigantism, whereas after closure it leads to acromegaly.

Acromegaly

• Acromegaly results from prolonged elevation of growth hormone in adults.
• It is most commonly caused by a somatotroph adenoma of the anterior pituitary.

Etiology

• Some tumors also increase prolactin secretion due to mixed cell proliferation.
• Rarely, excess hypothalamic growth hormone releasing hormone may contribute.

Features

• Clinical features include enlargement of hands and feet and prognathism.
• Facial bones become thickened, producing characteristic coarse facial features.
• Soft tissue growth leads to macroglossia and increased skin thickness.
• Visceromegaly affects organs such as liver, heart, and kidneys.
• Joint changes result in osteoarthritis and reduced mobility.
• Metabolic disturbances include glucose intolerance and insulin resistance.
• Enlargement of bones occurs in thickness rather than length due to fused epiphyses.
• Pituitary tumor expansion may compress the optic chiasma, causing bitemporal hemianopia.
• Headache is a common associated symptom due to increased intracranial pressure.

Management

• Diagnosis is based on clinical features, elevated growth hormone levels, and imaging studies such as magnetic resonance imaging.
• Measurement of insulin like growth factor one improves diagnostic accuracy.
• Management includes surgical removal of the tumor as the primary treatment.
• Additional therapies may include radiotherapy or medications to suppress hormone secretion.

Gigantism

Gigantism results from excess growth hormone secretion before epiphyseal closure, leading to excessive linear growth.

Causes

• It is commonly caused by a pituitary adenoma of somatotroph cells.
• Rarely, hypothalamic tumors increase growth hormone releasing hormone and contribute to the disorder.

Features

• Gigantism presents with excessive linear growth due to increased activity at epiphyseal plates before closure.
• Individuals develop abnormally tall stature with proportional body enlargement.
• Many features resemble acromegaly, except typical facial changes are less prominent.

Management

• Diagnosis is based on clinical features, elevated growth hormone, and imaging of pituitary tumors.
• Early surgical removal of the tumor is the primary treatment and can be curative.

Hyposecretion of GH

• Growth hormone deficiency leads to impaired growth, commonly presenting as dwarfism.
• Causes include reduced hypothalamic stimulation, pituitary failure, decreased hepatic production of insulin like growth factor one, or defective hormone receptors.

Pituitary Dwarfism

• Pituitary dwarfism is characterized by proportionate short stature and delayed skeletal maturation.
• Muscle mass, bone density, and cardiac function are reduced.
• Cognitive function is usually normal, which helps distinguish it from hypothyroid-related growth disorders.
• Diagnosis is based on low circulating growth hormone or insulin like growth factor levels.
• Early recognition is important for effective management.
• Treatment involves administration of growth hormone therapy, which improves growth outcomes when started early.

Other Hormones

Prolactin

Prolactin is a peptide hormone that primarily stimulates milk synthesis and supports mammary gland development. It also influences reproductive function and modulates certain immune responses.

Source

• It is secreted by lactotroph cells of the anterior pituitary, which constitute about 10 to 25 percent of endocrine cells.
• The number of lactotrophs increases during pregnancy, lactation, and with estrogen exposure.

Structure

Prolactin is a polypeptide of 198 amino acids with structural similarity to growth hormone.

Synthesis

It is synthesized as a precursor molecule, processed, and stored in secretory granules before release.

Regulation of Secretion

• Secretion rises progressively during late pregnancy and peaks at term.
• Elevated estrogen levels increase lactotroph number and enhance responsiveness to stimulatory signals.

Factors that Increase Prolactin Secretion

Factors that increase secretion include thyrotropin releasing hormone, pregnancy, breastfeeding, sleep, stress, serotonin, opioids, oxytocin, and certain medications that block dopamine action.

Factors that Decrease Prolactin Secretion

• Dopamine is the principal inhibitory regulator of prolactin secretion.
• Dopamine agonists suppress, whereas dopamine antagonists enhance prolactin release.
• Somatostatin and gamma aminobutyric acid also inhibit secretion. ·  Prolactin participates in feedback regulation by stimulating dopamine release, which in turn suppresses further secretion. This tight regulation ensures appropriate lactation while preventing excessive hormone production.

Mechanism of Action

• Prolactin acts by binding to specific membrane receptors structurally similar to growth hormone receptors. This interaction activates intracellular tyrosine kinase pathways.
• The Janus kinase signal transducer and activator of transcription pathway is stimulated.
• Activated transcription factors increase deoxyribonucleic acid and messenger ribonucleic acid synthesis. This enhances protein synthesis in target cells. It promotes formation of casein, lipids, and lactose, leading to milk production.

Physiological Effects

Effects on Milk Synthesis and Secretion

• Prolactin primarily stimulates milk synthesis in the mammary glands.
• Its secretion increases during pregnancy and lactation to support breastfeeding.

Effects on Breast Development

• It promotes breast development by inducing proliferation of glandular tissue.
• Along with estrogen and progesterone, it enhances ductal growth and branching.
• It also stimulates formation of alveoli, which are responsible for milk production.
• During lactation, prolactin acts with insulin and cortisol to increase milk production and secretion.
• These coordinated hormonal actions ensure effective nourishment of the newborn.

Effects on Reproduction

In Females

• Prolactin suppresses hypothalamic gonadotropin releasing hormone, reducing luteinizing hormone and follicle stimulating hormone levels.
• In females, this leads to lactational amenorrhea and prevents ovulation during breastfeeding. It also influences maternal behavior and reduces libido.

In Males

In males, elevated prolactin impairs spermatogenesis and may reduce reproductive function.

Effects on Immunity

• Prolactin is produced by immune cells and increases during pregnancy.
• It contributes to immune tolerance, supporting acceptance of the fetus by the maternal immune system.

Effects on Liver

• In the liver, prolactin stimulates production of intermediary growth factors such as synlactin. These factors resemble somatomedins and may promote tissue growth.
• Thus, prolactin indirectly supports growth and metabolic functions.

Clinical Correlation

Amenorrhea-Galactorrhea Syndrome

• Amenorrhea galactorrhea syndrome results from excess prolactin secretion, commonly due to pituitary or hypothalamic tumors.
• Elevated prolactin suppresses gonadotropin releasing hormone, leading to amenorrhea and infertility.
• Milk secretion occurs in the absence of pregnancy.
• Diagnosis is confirmed by high plasma prolactin levels and imaging studies.
• Treatment with dopamine agonists reduces prolactin levels and restores reproductive function.

Thyroid Stimulating Hormone

Structure

• Thyroid stimulating hormone is a glycoprotein that regulates growth and activity of the thyroid gland. It controls synthesis and release of thyroxine and triiodothyronine.
• It consists of two subunits, alpha and beta. The alpha subunit is common to luteinizing hormone and follicle stimulating hormone. The beta subunit provides hormonal specificity.
• The hormone has a molecular weight of about 28,000 and functions through receptor mediated mechanisms.

Source

Thyroid stimulating hormone is secreted by thyrotroph cells of the anterior pituitary, comprising about 3 to 5 percent of pituitary cells. These cells develop during early fetal life, and fetal thyroid function begins under their influence.

Synthesis

• The hormone is synthesized as a preprohormone, which is processed into a prohormone and then the active form.
• The alpha and beta subunits are produced separately from distinct genetic templates.
• Each subunit is translated from different messenger ribonucleic acid molecules.
• The subunits undergo glycosylation in the rough endoplasmic reticulum, where carbohydrate groups are added.
• Further modification occurs in the Golgi apparatus with addition of sialic acid and sulfate groups. These modifications allow proper assembly of the two subunits into the functional hormone.
• The completed hormone is stored in secretory granules within thyrotroph cells.
• Excess alpha subunits may also be stored and released along with the hormone. This regulated synthesis ensures effective control of thyroid gland function and hormone secretion.

Regulation of Secretion

• Thyroid stimulating hormone secretion normally ranges from about 0.3 to 5 micro units per milliliter. It is primarily stimulated by thyrotropin releasing hormone from the hypothalamus.
• Somatostatin and dopamine inhibit its release.
• Thyroid hormones exert negative feedback by suppressing hypothalamic and pituitary activity.
• Secretion shows diurnal variation, with higher levels during the night.
• Cortisol and growth hormone can also reduce thyroid stimulating hormone secretion.

Mechanism of Action

Thyroid stimulating hormone acts on thyroid follicular cells by increasing intracellular cyclic adenosine monophosphate, which activates enzymatic processes.

Functions

• It promotes iodide uptake and enhances its incorporation into thyroid hormones.
• It stimulates synthesis and secretion of thyroglobulin into the follicular lumen.
• It facilitates coupling reactions required for formation of thyroid hormones.
• It increases endocytosis of colloid and release of thyroxine and triiodothyronine into circulation.
• It also enhances blood flow and metabolic activity of the thyroid gland.
• Prolonged stimulation leads to growth and hypertrophy of thyroid tissue.

Applied Physiology

• Deficiency of thyroid stimulating hormone due to pituitary disorders results in secondary hypothyroidism with reduced thyroid activity.
• Chronic excess secretion causes enlargement of the thyroid gland, known as goiter.

Adrenocorticotropic Hormone

• Adrenocorticotropic hormone regulates growth and activity of the adrenal cortex.
• It primarily stimulates secretion of cortisol and is essential in stress responses.

Source and Structure

• It is secreted by corticotroph cells of the anterior pituitary, comprising about 10 to 20 percent of cells.
• It is a small peptide hormone with 39 amino acids and a molecular weight of approximately 4500.

Synthesis

• Adrenocorticotropic hormone is synthesized as part of a larger precursor called proopiomelanocortin in corticotroph cells. This precursor is cleaved to produce adrenocorticotropic hormone and other peptides such as beta lipotropin.
• In humans, adrenocorticotropic hormone contains a sequence similar to melanocyte stimulating hormone, giving it mild pigmentary activity.
• The intermediate lobe is poorly developed in humans, so melanocyte stimulating hormone production is limited.

Circadian Rhythm of ACTH Secretion

• Secretion occurs in a pulsatile manner, driven by intermittent release of corticotropin releasing hormone.
• A distinct circadian rhythm is present, with maximum secretion in the early morning. Levels begin to rise before awakening, peak between 7 and 10 in the morning, and decline by midday. A smaller rise may occur in the late afternoon. Secretion is lowest during deep sleep, especially around midnight.
• The pattern is influenced by the sleep wake cycle and internal biological clock located in the hypothalamus. Individuals with altered sleep patterns show reversal of this rhythm.
• Adrenocorticotropic hormone secretion closely parallels glucocorticoid release from the adrenal cortex.
• This coordinated rhythm is important for maintaining metabolic balance and stress response.

Regulation of ACTH Secretion

• Adrenocorticotropic hormone secretion is primarily regulated by corticotropin releasing hormone from the hypothalamus.
• Antidiuretic hormone also enhances its release, especially during stress.
• Corticotropin releasing hormone additionally increases sympathetic activity, blood pressure, and arousal.
• Factors that increase secretion include stress, hypoglycemia, infection, trauma, surgery, anxiety, and sleep wake transitions.
• Neurotransmitters such as serotonin and acetylcholine, along with interleukins and gastrointestinal hormones, also stimulate secretion.
• Inhibitory factors include cortisol, adrenocorticotropic hormone itself, somatostatin, gamma aminobutyric acid, natriuretic peptides, and opioids.
• Cortisol exerts strong negative feedback at both hypothalamic and pituitary levels.

ACTH and Stress

• Stress strongly activates the hypothalamo pituitary adrenal axis. It increases corticotropin releasing hormone output, leading to elevated adrenocorticotropic hormone levels. This results in rapid rise in glucocorticoid secretion from the adrenal cortex.
• Neural inputs from higher brain centers stimulate hypothalamic nuclei during stress. These signals can override normal feedback inhibition by cortisol.
• With prolonged stress, glucocorticoid levels remain elevated and feedback control resets to a higher level. This adaptive response helps maintain metabolic stability during sustained stress conditions.

Mechanism of Action

Adrenocorticotropic hormone acts on target cells by increasing intracellular cyclic adenosine monophosphate, which activates steroid synthesis.

Functions

• It stimulates secretion of cortisol and other adrenal steroids, with predominant effect on glucocorticoids.
• It promotes hypertrophy of adrenal cortical cells, enhancing functional capacity.
• It possesses mild melanocyte stimulating activity, leading to increased melanin production and skin pigmentation.
• Receptors are present in the brain and gastrointestinal tract, where it may act as a local signaling molecule.
• It also modulates immune responses by influencing cytokine release from lymphocytes.

LH and FSH

Luteinizing hormone and follicle stimulating hormone are gonadotropins that regulate gonadal growth, puberty, and sex steroid secretion.

Source and Structure

• They are secreted by gonadotroph cells of the anterior pituitary, comprising about 10 to 15 percent of pituitary cells.
• Both hormones are glycoproteins composed of alpha and beta subunits.
• The alpha subunit is common to other glycoprotein hormones, while the beta subunit provides specificity.
• Follicle stimulating hormone contains 111 amino acids in the beta subunit, whereas luteinizing hormone contains 121 amino acids.

Synthesis

• Carbohydrate components contribute to biological activity and stability.
• They are synthesized from separate genes encoding alpha and beta subunits.
• Post translational glycosylation modifies their activity and circulating half life.

Regulation of Secretion

• Secretion is primarily regulated by gonadotropin releasing hormone from the hypothalamus. This secretion is pulsatile and influenced by neural, emotional, and environmental factors.
• Norepinephrine stimulates, whereas dopamine and endogenous opioids inhibit hypothalamic release.
• Gonadal hormones regulate secretion through feedback mechanisms.
• Testosterone in males and estrogen in females suppress gonadotropin release.
• Inhibin selectively inhibits follicle stimulating hormone secretion.
• Activin enhances synthesis and release of follicle stimulating hormone.
• Follistatin binds activin and reduces its stimulatory effect.
• Prolactin suppresses gonadotropin secretion by inhibiting hypothalamic signaling.
• This coordinated regulation ensures normal reproductive function, gametogenesis, and hormonal balance.

Functions

Luteinizing hormone and follicle stimulating hormone act by increasing intracellular cyclic adenosine monophosphate levels.