The pituitary gland or the hypophysis cerebri is a vital structure of the human body as it performs essential functions for sustaining life. It has the pseudonym of “the master gland.” The location of the gland is within the sella turcica of the sphenoid bone. It is made up of two distinct regions called the anterior lobe and posterior lobe, which are functionally active. There is an intermediate lobe in between them. The anterior lobe secretes the majority of hormones from the pituitary gland, which are under the regulation of the hormones secreted from the hypothalamus.
Structure and Function
GROSS ANATOMY OF THE PITUITARY GLAND
The pituitary gland undergoes rapid growth from birth to adult life to reach a weight of 500 mg. The adult gland has an anteroposterior diameter of 8 mm and a transverse diameter of 12 mm. There is a discrepancy between the size of the gland in males and females. During pregnancy, it almost doubles in size as the pars distalis enlarges. Pars distalis is a part of the anterior pituitary. It is bound superiorly by the diaphragm sellae, anteroinferior by the sphenoid sinus, and laterally by the cavernous sinus. The optic chiasm lies anterosuperior to the gland. The tuber cinereum and median eminence of the hypothalamus give origin to an infundibulum. The tubular infundibulum connects the hypophysis to the brain. Due to the dual origin of the gland, they have a unique histological appearance. They are made up of anatomically and functionally distinct lobes called the anterior lobe (adenohypophysis), posterior lobe (neurohypophysis), and intermediate lobe.[rx][rx]
The pituitary gland is within the sella turcica or the hypophyseal fossa. This structure is present near the center at the base of the cranium and is fibro-osseous. The anatomical boundaries of the gland have clinical and surgical significance. Sella turcica is a concave indentation in the sphenoid bone. The reflections of the dura bound the fossa laterally and superiorly.
Sellar Anatomy
The bony walls of the sella turcica surround the fossa in the anterior, posterior, and inferior margins. The pituitary gland, along with the sella turcica, constitutes the sellar region. Tuberculum sellae makes up the anterior wall, and dorsum sellae makes up the posterior bony wall. Anterosuperior to the tuberculum is the sulcus chiasmaticus. The margins of the dorsum sellae form rounded structures called the posterior clinoid process. The anterolateral margin of the sella turcica forms the anterior clinoid process. These two clinoid processes aids in the attachment of the dural folds. The roof of the sphenoid sinus forms the floor of the pituitary fossa. The diaphragm sellae is a dural fold with a central aperture, and it covers the sella turcica as a roof incompletely. The adenohypophysis is separated from the optic chiasm by the diaphragm. It is continuous with the dura. The pituitary stalk and the blood vessels travel via the central aperture.
Parasellar and Suprasellar Anatomy
The cavernous sinus and the suprasellar cistern encompasses the parasellar region. The lateral walls of the pituitary fossa are made up of dura mater, and it contains the cavernous sinus. The cavernous sinus consists of the internal carotid artery, sympathetic fibers, cranial nerves III, IV, V, and VI. The suprasellar cistern encompasses the optic chiasm, part of the third ventricle, hypothalamus, and the tuber cinereum. This tuber cinereum is a gray matter lamina. Researchers identified an increased concentration of type IV collagen in the pituitary gland and surrounding tissue, including the capsule. This tissue has clinical importance as it has implications in the adenoma progression and invasion of adjacent structures.[rx][rx]
ANTERIOR PITUITARY GLAND
MICROSCOPIC ANATOMY
The adenohypophyses constitute well-defined acini, consisting of cells that produce and secrete hormones. There are six cell lines, of which five are hormone-producing cell types called somatotrophs, lactotrophs, corticotrophs, thyrotrophin, and gonadotrophs. Also, a nonhormone producing sixth cell type in the anterior pituitary called the folliculostellate cells. The anterior pituitary gland encompasses the following structures:
- Pars Distalis: This is located at the distal part of the gland, and most of the hormones get secreted from this region. It forms the major bulk of the anterior pituitary. It is composed of follicles of varied sizes. Based on the staining methods used, the hormone-producing cells are classified below:
- Acidophils: They are composed of polypeptide hormones, and their cytoplasm stains red to orange in color. The somatotrophs and lactotrophs are the acidophils.
- Basophils: They are composed of glycoprotein hormones and their cytoplasm stain blue to purple in color. The thyrotrophs, gonadotrophs, and corticotrophs are the basophils.
- Chromophobes: They do not stain well. They may represent stem cells that are yet to differentiate into mature hormone-producing cells.
- Pars Tuberalis: The tubular stalk is divided into pars tuberalis anteriorly and posteriorly. It extends from the pars distalis. The pars tuberalis encircles the infundibular stem, which is composed of unmyelinated axons from the hypothalamic nuclei. The hormones oxytocin and vasopressin accumulate in these axons, forming ovoid eosinophilic swellings along the infundibular stem. They make up the ‘herring bodies.’
- Pars Intermedia: This is present between the pars distalis and the posterior pituitary gland. It is made up of follicles containing a colloidal matrix and includes the remainder of the Rathke’s pouch cleft. Though it is mostly nonfunctioning, they produce melanocyte-stimulating hormone, endorphins and have some pituitary stem cells.
The hypothalamus is where the initial primary signal hormones get synthesized to stimulate the pituitary gland. Their synthesis is in the cell body of the neurons following which the axons project to terminate at the gland in the fenestrated portal capillaries. Then they travel via the bloodstream to the pituitary gland to stimulate the specific cells or inhibit it.
FUNCTION
The following are the hormones produced and secreted from the anterior pituitary.
- Adrenocorticotropic Hormone (ACTH) – The release of this hormone from the gland is in response to the corticotropin-releasing hormone (CRH) from the hypothalamus. The CRH reaches the target location via the portal system and cleaves the proopiomelanocortin (POMC) into three major substances that are the ACTH, melanocyte-stimulating hormone, beta-endorphins. They then travel to reach the adrenal cortex, via the bloodstream to facilitate the release of cortisol. The negative feedback from the cortisol regulates the CRH and ACTH. They aid in the secretion of glucocorticoids during stress.
- Prolactin (PRL): This hormone is under the direct control of the hypothalamus. Dopamine inhibits the release of prolactin. The suckling of the baby in the postpartum period will inhibit the release of dopamine, thus disinhibiting prolactin release. When there is a drop in the dopamine levels due to disease or drugs, the patient will present with galactorrhea. Their primary function is to stimulate the growth of the mammary glands and participate in milk production.
- Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH): The gonadotropin-releasing hormone (GnRH) that is secreted from the hypothalamus acts on the gonadotropin cells to secrete the LH and FSH. In males, the LH acts on the Leydig cells and secretes testosterone from the testes. The FSH acts on the Sertoli cells and secretes inhibin B for spermatogenesis. In females, the LH acts on the ovaries to initiate the production of the steroid hormone, and its surge causes ovulation. FSH acts on the granulosa cells and initiates follicular development for ovulation by the mature Graafian follicle. The steroid sex hormones regulate the LH and FSH through negative feedback.
- Growth Hormone or Somatotropin (GH): The GH gets secreted from the somatotrophs in response to the growth hormone-releasing hormone released from the hypothalamus. GH has anabolic properties and stimulates the growth of the cells in the body. The GH release is under the regulation of the negative feedback from the increased blood levels of GH and IGF-1.
- Thyroid Stimulating Hormone (TSH): TSH secretion from the gland thyrotropic occurs in response to the thyrotropin-releasing hormone from the hypothalamus. This TSH acts on the thyroid gland to stimulate the release of T3 and T4. The TSH gets regulated by the blood levels of T3 and T4.[rx][rx][rd][rx]
POSTERIOR PITUITARY GLAND
MICROSCOPIC ANATOMY
This portion of the gland is a specialized neuroendocrine structure. The posterior pituitary is a combination of pars nervosa and the infundibular stalk. They contain axons that have originated from hypothalamic neurons, specifically the axon terminals of the magnocellular neurons of the paraventricular and supraoptic nuclei. Glial cells called pituicytes encircle the axons. The pituicytes have elongated processes that run along with the axons; these are absent in a typical astrocyte and is due to the transcription factor expression TTF-1. The axons together form the hypothalamohypophyseal tract, which terminates near the posterior lobe sinusoids. The terminals of the axons are close to the blood vessels to aid in the secretion of the hormones. The precursor hormones are packed into secretory granules, called the herring bodies. These precursor hormones then get cleaved during transport to the posterior pituitary. Neurophysins are proteins that are essential for the posttranslational processing of hormones. The posterior pituitary is not glandular, like the anterior pituitary. Thus they do not synthesize hormones.
FUNCTION
The following are the two hormones released from the posterior pituitary.
- Oxytocin: They participate in the milk let-down or milk ejection reflex during lactation, myoepithelial, and smooth muscle contraction, uterine contraction. This hormone is available for exogenous administration to patients with postpartum hemorrhage. Five IU of oxytocin is the recommended intravenous injection dosage to prevent postpartum hemorrhage, and it is given following the delivery of the anterior shoulder of the fetus.[rx]
- Arginine Vasopressin (AVP) or Antidiuretic Hormone (ADH): These hormones aid in the regulation of water content and prevents water depletion. It maintains the tonicity of the blood and blood pressure during an event of volume loss. The vascular smooth muscles express the V1 receptors, which, in response to the AVP, causes arteriolar contraction. The renal collecting duct and the tubular epithelium express V2 receptors, which in response to AVP, upregulate the aquaporin two channels and increases free water reuptake.[rx][rx][rx][rx]
Cellular
The hormones of the pituitary gland are protein or polypeptide in nature and vary in complexity.
Anterior Pituitary Hormones
Human Growth Hormone
Human growth hormone (HGH), also known as somatotropin, is a protein of 191 amino acid single chain polypeptides secreted by the acidophilic somatotropic cells of the anterior pituitary gland.[rx] Its levels in the body are under tight regulation by the hypothalamus mediators, growth hormone-releasing hormone (GHRH), and growth hormone-inhibiting hormone (GHIH or somatostatin).
Prolactin
Prolactin is a protein hormone secreted by the acidophilic lactotroph cells of the anterior pituitary gland. Chemically, prolactin is similar to a growth hormone composing of 199 amino acids, and forms after a 28-amino acid signal peptide are proteolytically cleaved from the prolactin prohormone (pre-prolactin).[rx] The secretion of prolactin by the anterior pituitary is tonically inhibited by dopamine from the tuberoinfundibular pathway of the hypothalamus and stimulated by thyrotropin-releasing hormone (TRH), estrogen, dopamine antagonist (antipsychotics), and multiple factors including suckling, stress, and sleep.
Follicle-stimulating Hormone (FSH) and Luteinizing Hormone (LH)
FSH and LH, also known as gonadotropins, are glycoprotein hormones secreted by the gonadotropin cells of the adenohypophysis. They are both glycoproteins made up of an alpha and beta subunit. The alpha subunits are identical between the two hormones, but the beta subunit of each is different and gives each hormone its biological specificity.[rx] Particularly, the alpha subunit of LH is made up of 92 amino acids, and the beta subunit contains 120 amino acids.[rx] The gonadotropic cells do not react well with acid or basic stains and thus appear either basophilic or chromophobic under the microscope.[rx] The secretion of these hormones is regulated by the release of gonadotropin-releasing hormone secreted by the hypothalamus.
Adrenocorticotrophic Hormone (ACTH)
The adrenocorticotrophic hormone is a polypeptide tropic hormone produced and secreted by the basophilic corticotropic cells of the anterior pituitary gland. ACTH is synthesized from Pro-opiomelanocortin (POMC) and consists of 39 amino acids. The hypothalamus-pituitary axis and secretion tightly regulate its production is in response to the corticotropin-releasing hormone.
Thyroid-stimulating Hormone (TSH)
Thyroid-stimulating hormone is a peptide hormone secreted by the basophilic thyrotropes of the anterior pituitary gland. It is composed of 1 alpha chain and one beta chain.[rx] The hypothalamus-pituitary axis regulates its release. The hypothalamus releases thyroid-releasing hormone (TRH), which stimulates thyrotrophs of the anterior pituitary to secrete TSH.
Posterior Pituitary Hormones
Vasopressin & Oxytocin
Vasopressin, also known as antidiuretic hormone (ADH), is synthesized in the supraoptic nuclei of the hypothalamus while oxytocin synthesis occurs in the paraventricular nuclei of the hypothalamus. Both the posterior pituitary hormones are packaged in secretory granules and move down the axon where they are stored in the Herring bodies. These bodies are neurosecretory granules that represent the terminal ends of the axons coming from the hypothalamus.
References