Hypothalamus and Pituitary Gland

1. Introduction to the Hypothalamus

• The hypothalamus is a small but critically important part of the brain that plays a central role in maintaining homeostasis by integrating autonomic, endocrine, and behavioral responses.
• Despite its small size (about 4 g), it influences nearly every system in the body, including temperature regulation, hunger, thirst, sleep–wake cycles, emotional behavior, and hormonal secretion via the pituitary gland.

Location and Anatomical Boundaries

The hypothalamus is located below the thalamus and forms the floor and part of the walls of the third ventricle.

• Superior (Above): Thalamus
• Inferior (Below): Extends to the base of the brain; bounded by the optic chiasm, infundibulum, and mammillary bodies
• Anterior: Optic chiasm and lamina terminalis
• Posterior: Midbrain tegmentum
• Lateral: Internal capsule and subthalamic region
• Medial: Third ventricle

Surface landmarks:

• Optic chiasm: Anterior to the hypothalamus
• Infundibulum (pituitary stalk): Connects hypothalamus to pituitary gland
• Mammillary bodies: Paired rounded structures marking the posterior limi

Subdivisions of the Hypothalamus

For descriptive purposes, the hypothalamus is divided into three anteroposterior regions and three mediolateral zones:

A. Anteroposterior Regions

1.     Anterior (Chiasmatic) Region:

• Located above the optic chiasm
• Includes the supraoptic, paraventricular, preoptic, and suprachiasmatic nuclei

2.     Tuberal (Middle) Region:

• Located above the tuber cinereum and infundibulum
• Includes the arcuate, ventromedial, and dorsomedial nuclei

3.     Posterior (Mammillary) Region:

• Located above and behind the mammillary bodies
• Includes the posterior nucleus and mammillary nuclei

B. Mediolateral Zones

1. Periventricular Zone: Thin strip along the third ventricle; contains neurons regulating endocrine functions
2. Medial Zone: Contains most hypothalamic nuclei; involved in integrating autonomic and endocrine responses
3. Lateral Zone: Contains medial forebrain bundle and scattered nuclei; involved in feeding and arousal

1.1. Major Hypothalamic Nuclei and Their Functions

Below is a summary of key hypothalamic nuclei, their locations, and functions:

1.2. Functions of the Hypothalamus

The hypothalamus serves as the control center linking the nervous system and endocrine system. Its major functions include:

1. Autonomic Nervous System Regulation

• Controls sympathetic and parasympathetic activity
• Influences heart rate, blood pressure, gastrointestinal motility, pupil size, sweating, and thermoregulation

2. Endocrine Control via the Pituitary

• Anterior pituitary: Releasing and inhibiting hormones from the arcuate and paraventricular nuclei regulate hormone secretion (e.g., CRH → ACTH; TRH → TSH; GnRH → LH/FSH).
• Posterior pituitary: ADH and oxytocin produced in the supraoptic and paraventricular nuclei are transported via axons to be released into circulation.

3. Thermoregulation

• Anterior region: Heat loss center (vasodilation, sweating)
• Posterior region: Heat conservation (vasoconstriction, shivering)

4. Regulation of Food and Water Intake

• Lateral zone: Feeding center – stimulation induces eating
• Ventromedial nucleus: Satiety center – stimulation inhibits eating
• Osmoreceptors in the anterior hypothalamus regulate thirst and ADH secretion

5. Circadian Rhythms

• Suprachiasmatic nucleus synchronizes body rhythms (sleep–wake cycles, hormone secretion) with the light–dark cycle

6. Emotional and Behavioral Responses

• Connections with the limbic system influence emotional expression, sexual behavior, and stress responses

7. Memory and Learning

• Mammillary bodies are part of the Papez circuit, essential for memory consolidation

1.3. Clinical Correlations

1.4. Introduction to the Pituitary Gland

The pituitary gland (hypophysis) is a small, oval endocrine organ situated at the base of the brain. It serves as the master gland, controlling multiple endocrine glands through its secretion of hormones.

It has two major parts with different embryological origins, anatomical structures, and functions:

1. Anterior Pituitary (Adenohypophysis) — glandular in nature, secretes multiple trophic hormones and is controlled by hypothalamic releasing/inhibiting hormones.
2. Posterior Pituitary (Neurohypophysis) — neural in origin, stores and releases hypothalamic hormones (ADH, oxytocin).

• The pituitary gland lies in the sella turcica, a depression in the sphenoid bone at the skull base.
• It is covered superiorly by a fold of dura called the diaphragma sellae, through which the infundibulum (pituitary stalk) passes.
• Superior: Optic chiasm
• Inferior: Sphenoid sinus
• Lateral: Cavernous sinuses (containing internal carotid artery, cranial nerves III, IV, V1, V2, VI)
• Posterior: Dorsum sellae

2. Anterior Pituitary (Adenohypophysis)

Introduction

• The anterior pituitary has no direct neural connection with the hypothalamus.
• Instead, it is regulated by hypothalamic releasing and inhibiting hormones transported through the Hypothalamo–Hypophyseal Portal veins or system (see figure in unit 1.4).
• This unconventional vascular connection between the hypothalamus and posterior pituitary ensures that minute quantities of hypothalamic hormones are carried in a concentrated form directly to their target cells in the anterior pituitary, and are not diluted out in the systemic circulation.

• Derived from Rathke’s pouch, an ectodermal outgrowth of the primitive oral cavity.
• Forms about 75% of the pituitary gland.
• Subdivisions:

Hypothalamic Control of the Anterior Pituitary

The anterior pituitary has no direct neural connection with the hypothalamus. Instead, it is regulated by hypothalamic releasing and inhibiting hormones transported through the hypophyseal portal system (see fig in section 1.4 and below)

• Arcuate nucleus (Tuberal region): major source of releasing/inhibiting hormones
• Paraventricular nucleus: secretes corticotropin-releasing hormone (CRH), thyrotropin-releasing hormone (TRH), and somatostatin
• Preoptic area: secretes gonadotropin-releasing hormone (GnRH)

• The anterior pituitary is controlled via releasing and inhibiting hormones produced in the hypothalamus. and
• These hormones are transported to the Anterior Pituitary through the hypothalamo-hypophyseal portal system.

• This is the only case in which hormones released into the blood do not go to the entire body

Hypothalamic Hormone	Effect on Anterior Pituitary
Corticotropin-releasing hormone (CRH)	Stimulate secretion of adrenocorticotropic Hormones (ACTH)
Gonadotropin-releasing hormone (GRH)	Stimulate secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH)
Prolactin-inhibiting hormone (PIH)	Inhibits prolactin secretion
Somatostatin	Inhibits secretion of growth hormone
Thyrotropin-releasing hormone (TRH)	Stimulates secretion of thyroid-stimulating hormone (TSH)
Growth hormone−releasing hormone (GHRH)	Stimulates growth hormone secretion

Hormone	Source Cells	Target Organ(s)	Main Function(s)
GH (Growth Hormone)	Somatotrophs	Liver, bone, muscle	Stimulates growth, protein synthesis, IGF-1 secretion
TSH (Thyroid-Stimulating Hormone)	Thyrotrophs	Thyroid gland	Stimulates T₃ and T₄ secretion
ACTH (Adrenocorticotropic Hormone)	Corticotrophs	Adrenal cortex	Stimulates cortisol production
LH (Luteinizing Hormone)	Gonadotrophs	Gonads	Ovulation, corpus luteum, testosterone secretion
FSH (Follicle-Stimulating Hormone)	Gonadotrophs	Gonads	Follicular growth, spermatogenesis
PRL (Prolactin)	Lactotrophs	Mammary glands	Milk production
MSH (Melanocyte-Stimulating Hormone)	Pars intermedia (rudimentary)	Skin melanocytes	Pigmentation (minor role in humans)

GH → Liver → Growth via IGF

ACTH → Adrenal Cortex → Cortisol release

TSH → Thyroid → Thyroid hormones (T3, T4)

FSH/LH → Gonads → Gametogenesis & sex hormones

PRL → Mammary glands → Milk production and growth of mammary glands

Feedback Control of Anterior Pituitary

Release of tropic hormones is controlled by the hypothalamus which is in turn controlled by the activity of the target glands.

Example: Hypothalamus-Pit-Thyroid Axis

Low levels of thyroxin in the blood stimulate the hypothalamus to secrete thyroid stimulating hormone releasing hormone into the hypophyseal portal system.

The portal system delivers this hormone to the secretory cells of the anterior pituitary which secrete thyroid stimulating hormone (TSH) into general systemic circulation in response.

The blood carries the TSH hormone to the thyroid gland which has cells with receptor proteins for TSH hormone.

Thyroid cells secrete thyroxin into the blood which carries it throughout the body.

Target cells all over the body respond by increasing oxidative RNA synthesis and metabolism.

Cells of the hypothalamus, however, respond to the elevated thyroxin levels by decreasing their production of thyroid stimulating hormone releasing hormone.

This causes the anterior pituitary to decrease production of TSH which in turn causes the thyroid to decrease production of thyroxin.

Blood levels of thyroxin decrease.

The final product regulates secretion of pituitary hormones.

Inhibition can occur at the hypothalamus or pituitary gland level, inhibiting secretion of releasing or stimulating hormones respectively.

3. Posterior Pituitary (Neurohypophysis)

• Derived from a downward extension of the diencephalon (neuroectoderm).
• Composed mainly of unmyelinated axons and pituicytes (glial-like cells).
• Subdivisions:
  • Pars nervosa (main body)
  • Infundibular stalk (connects to hypothalamus)
  • Median eminence (interface with hypothalamus)

4. Comparative Summary Table

5. Regulatory Pathways – Hormonal Control of Growth, Metabolism, and Reproduction

• Hypothalamic-pituitary-thyroid axis: TRH → TSH → T3/T4 → metabolism.

• Hypothalamic-pituitary-adrenal axis: CRH → ACTH → cortisol → stress response.

• Hypothalamic-pituitary-gonadal axis: GnRH → LH/FSH → estrogen/testosterone → reproduction

6. Clinical Correlations

• Hypersecretion of GH leads to cause gigantism in children and acromegaly in adult.
• Hyposecretion of GH results in dwarfism during childhood.

7. Key Points Summary

• The anterior pituitary is glandular, controlled by hypothalamic releasing/inhibiting hormones via the portal system, and secretes trophic hormones.
• The posterior pituitary is neural, acts as a storage and release site for hypothalamic hormones ADH and oxytocin.
• Hypothalamic nuclei:
  • Arcuate & paraventricular (releasing hormones) → anterior pituitary regulation
  • Supraoptic & paraventricular (ADH/oxytocin) → posterior pituitary outpu
  • Disorders can involve hypersecretion, hyposecretion, or mass effects