Hypothalamus & Pituitary Gland

The Pituitary Gland and Hypothalamus The pituitary gland (hypophysis) is located at the base of the brain, immediately below the hypothalamus. It is connected to the hypothalamus by a pituitary stalk The pituitary gland (hypophysis) is located at the base of the brain, immediately below the hypothalamus. It is connected to the hypothalamus by a pituitary stalk. It comprises 2 lobes: anterior (adenohypophysis) and posterior (neurohypophysis).   The posterior pituitary is an extension of the hypothalamus, and consists of neural tissue. The cell bodies of certain neurons which are located in the hypothalamus send their axons down the stalk to the posterior pituitary, where they end close to capillaries. The anterior pituitary in contrast has no direct neural connection to the brain. Its functional connection to the hypothalamus is through blood: blood from the hypothalamus drains into capillaries of the anterior pituitary. This allows “controlling hormones” to travel directly from the hypothalamus to the anterior pituitary.

Pituitary-Hypothalamic relationships The pituitary gland comprises 2 lobes: posterior (neurohypophysis) and anterior (adenohypophysis) The posterior pituitary is an extension of the hypothalamus, and consists of neural tissue The hormones are synthesised in the hypothalamus neurons. They are transported down the axons and stored in vesicles in the axon ending located in the posterior pituitary Nerve impulses travel down axons into the posterior pituitary. This causes the release of the vesicles of hormones into the blood stream at the posterior pituitary

Pituitary-Hypothalamic relationships The anterior pituitary has no direct neural connection to the brain. ⟶ Blood from the hypothalamus drains into capillaries of the anterior pituitary ⟶ releasing and release-inhibiting hormones are carried in the blood to the anterior pituitary to regulate hormone release

Hormone Secretion

Morphology The pituitary gland (hypophysis) is located in a small depression in the sphenoid bone, the sella turcica, just beneath the hypothalamus It is connected to the hypothalamus by a thin stalk called the infundibulum Sella turcica

Histology of the Anterior Lobe Most of the cells in the anterior lobe (adenohypophysis) contain secretory granules, although some are only sparsely granulated Based on their characteristic staining with standard histochemical dyes and immunofluorescent stains, it is possible to identify the cells that secrete each of the pituitary hormones

Histology of the Posterior Lobe The posterior lobe (neurohypophysis) consists of two major portions: the infundibulum, or stalk, and the infundibular process, or neural lobe The posterior lobe is richly endowed with fibers The cell bodies from which these fibers arise are located in the hypothalamus Secretory material synthesized in cell bodies in the hypothalamus is transported down the axons and stored in in the posterior lobe

Physiology of the Posterior Pituitary The posterior pituitary gland secretes two hormones which are: oxytocin , increase uterine contractions during parturition Contraction of mammary glands to secret milk and vasopressin or arginine vasopressin (AVP) (or Antidiuretic Hormone ‘ADH’) contract vascular smooth muscle and thus raise blood pressure promote reabsorption of water by renal tubules

Physiology of the Posterior Pituitary Oxytocin and AVP are stored in and secreted by the posterior pituitary gland, but are synthesized by the hypothalamus

Regulation of Posterior Pituitary Function Regulation of oxytocin secretion showing a positive feedback arrangement. Increased blood osmolality or decreased blood volume are sensed in the brain or thorax, respectively, and increase vasopressin secretion.

Posterior Pituitary hormones The posterior pituitary secretes two peptide hormones: ⟶ oxytocin (OT) ⟶ antidiuretic hormone (ADH); also known as vasopressin

Oxytocin Stimulates uterine contractions during childbirth by mobilizing Ca2+ through a second-messenger system Also triggers milk ejection (“letdown” reflex) in women producing milk Plays a role in sexual function in males and females Certain images and/or photos on this page are the copyrighted property of 123RF Limited, their Contributors or Licensed Partners and are being used with permission under license. These images and/or photos may not be copied or downloaded without permission from 123RF Limited.

Antidiuretic Hormone (ADH) Osmoreceptors in the hypothalamus respond to changes in the solute concentration of the blood plasma If solute concentration is high ⟶ Osmoreceptors depolarize and transmit impulses to hypothalamic neurons ⟶ ADH is synthesized and released, inhibiting urine formation by the kidneys

Physiology of the Anterior Pituitary Gland There are six anterior pituitary hormones whose physiological importance is clearly established They include the hormones that govern the function of the: thyroid and adrenal glands, the gonads, the mammary glands, and bodily growth

Hormones of the Anterior Pituitary Gland All the anterior pituitary hormones are proteins or glycoproteins They are divided into 3 categories according to structure similarity: Glycoprotein Hormones Growth hormone and prolactin Adrenocorticotropin family

Glycoprotein Hormones Target Major actions in humans Thyroid-stimulating hormone (TSH), also called thyrotropin Thyroid gland Stimulates synthesis and secretion of thyroid hormones Follicle-stimulating hormone (FSH) Ovary Stimulates growth of follicles and estrogen secretion Testis Acts on Sertoli cells to promote maturation of sperm Luteinizing hormone (LH) Stimulates ovulation of ripe follicle and formation of corpus luteum; stimulates estrogen and progesterone synthesis by corpus luteum Stimulates interstitial cells of Leydig to synthesize and secrete testosterone

Growth Hormone and Prolactin Somatotropes (GH producing cells) are by far the most abundant anterior pituitary cells, and account for at least half the cells Structurally, prolactin (PRL) is closely related to GH Hormone Target Major actions in humans Growth hormone (GH), also called somatotropic hormone (STH) Most tissues Promotes growth in stature and mass; stimulates production of insulin-like growth factor (IGF-I); stimulates protein synthesis; usually inhibits glucose utilization and promotes fat utilization Prolactin Mammary glands Promotes milk secretion and mammary growth

Adrenocorticotropin Family The ACTH related peptides constitute a family because: they contain regions of homologous amino acid sequences, which may have arisen through exon duplication, and because they all are encoded in the same gene Hormone Target Major actions in humans Adrenocorticotropic hormone (ACTH), also known as adreno-corticotropin or corticotropin Adrenal cortex Promotes synthesis and secretion of adrenal cortical hormones β-Lipotropin Adipose Tissue Physiological role not established

Regulation of Anterior Pituitary Function Secretion of the anterior pituitary hormones is regulated by: the central nervous system provides the primary drive for secretion and hormones produced in peripheral target glands and peripheral input plays a secondary, though vital, role in modulating secretory rates Secretion of all the anterior pituitary hormones except PRL declines severely in the absence of stimulation from the hypothalamus as can be produced when the pituitary gland is removed surgically from its natural location and reimplanted at a site remote from the hypothalamus PRL secretion is normally under tonic inhibitory control by the hypothalamus

Feedback Control of Anterior Pituitary Function Environmental factors may increase or decrease pituitary activity by increasing or decreasing hormone secretions from hypothalamus Pituitary secretions increase the secretion of target gland hormones, which may inhibit further secretion by acting at either the hypothalamus or the pituitary Pituitary hormones may also inhibit their own secretion by a short feedback loop

Anterior Pituitary hormones All are proteins All except GH activate cyclic AMP second-messenger systems at their targets TSH, ACTH, FSH, and LH are all tropic hormones (regulate the secretory action of other endocrine glands)

Growth Hormone (GH) Stimulates cell division - targets bone and skeletal muscle Promotes protein synthesis and encourages use of fats for fuel Most effects are mediated indirectly by insulin-like growth factors (IGFs) Like several other hormones, growth hormone is secreted in a rhythmic fashion, with secretion occurring mainly during the early stages of sleep at night. Its secretion is also increased during exercise, stress and fasting.   In old age, the level of growth hormone decreases; this explains in part the loss of muscle mass and muscle strength in later years, as well as thinning of the skin. The effect of growth hormone is largely indirect: when growth hormone binds to target cells, they secrete the protein “insulin-like growth factor 1” (IGF-1) and it is this substance which directly causes most of the effects of growth hormone.

Thyroid-Stimulating Hormone http://www.youtube.com/watch?v=hLeBNyB1qKU Thyroid-Stimulating Hormone Produced by the anterior pituitary Stimulates the normal development and secretory activity of the thyroid Regulation of TSH release ⟶ Stimulated by thyrotropin-releasing hormone (TRH) ⟶ Inhibited by rising blood levels of thyroid hormones that act on the pituitary and hypothalamus This hormone stimulates the thyroid gland to secrete thyroid hormones. The secretion of TSH is subject to negative feedback by high blood levels of thyroid hormones; this stabilises blood levels of both TSH and thus of the thyroid hormones themselves. Conversely, high levels of TSH are elicited by low blood levels of thyroid hormones.

Adrenocorticotropic Hormone (ACTH) Secreted by the anterior pituitary Stimulates the adrenal cortex to release cortisol and aldosterone (to a lesser extent) Regulation of ACTH release ⟶ triggered by hypothalamic corticotropin-releasing hormone (CRH) in a daily rhythm ⟶ internal and external factors such as fever, hypoglycaemia, and stressors can alter the release of CRH

Gonadotropins Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) secreted by the anterior pituitary ⟶ FSH stimulates gamete (egg or sperm) production ⟶ LH promotes production of gonadal hormones

Prolactin (PRL) Secreted by the anterior pituitary Stimulates milk production Regulation of PRL release Primarily controlled by prolactin-inhibiting hormone (PIH) (dopamine) Blood levels rise toward the end of pregnancy Suckling stimulates PRH release and promotes continued milk production

Hypophysiotropic hormones Physiological actions of the pituitary

Pituitary & Hypothalamic Disorders Hypothalamic-pituitary lesions present with a variety of signs, including pituitary hormone: hypersecretion and hyposecretion, sellar enlargement, and visual loss

Pituitary & Hypothalamic Disorders In adults, the most common cause of hypothalamic-pituitary dysfunction is a pituitary adenoma, of which the great majority are hypersecreting Thus, the earliest symptoms of such tumors are due to endocrinologic abnormalities and include: Early manifestation Hypogonadism, the most frequent diminished functional activity of the gonads Late manifestation in patients with larger tumors or suprasellar extension sellar enlargement headache and visual loss,

Gonadotrophins Disorders Hyposecretion  leads to amenorrhoea, sterility and loss of sexual potency. In the young, the sex organs and secondary sexual characteristics fail to develop (delayed puberty) Hypersecretion  extremely rare, in children it could lead to sexual precocity (excessive premature development)

Thyrotrophin Disorders Hyposecretion  produces a clinical picture similar to primary thyroid deficiency Hypersecretion  gives the symptoms of hyperthyroidism similar to Graves’ disease

Corticotrophin Disorders Hyposecretion  rare causes failure of cortisol secretion, a general lack of health and well being, a reduced response to stress and skin depigmentation Hypersecretion  due to a pituitary microadenoma, will result in Cushing’s syndrome

Prolactin Disorders Hyposecretion Hypersecretion leads to failure of lactation in women Hypersecretion  may result from a pituitary tumour principal symptoms are infertility and menstrual complaints in men, decreased libido, inadequate sperm production and impotence, whereas in women, there may be a complete lack of menstruation inappropriate (non-pregnant) milk production Dopamine, some drugs

GHRH Disorders Hyposecretion Hypersecretion caused by hypothalamic or pituitary dysfunction In childhood this leads to impairment of growth (dwarfism) Hypersecretion This usually results from a benign pituitary tumour In young patients, this leads to gigantism In adults, leads to acromegaly

Vasopressin Disorders Hyposecretion  caused by damage or dysfunction of the hypothalamus, can lead to diabetes insipidus,  excessively large amounts of dilute urine (10–15 liters/day) are produced by the kidneys Hypersecretion  rare condition of inappropriate AVP production is known as syndrome of inappropriate ADH (SIADH)

Hypopituitarism Hypopituitarism is manifested by diminished or absent secretion of one or more pituitary hormones Hypopituitarism is either: a primary event caused by destruction of the anterior pituitary gland or a secondary phenomenon resulting from deficiency of hypothalamic stimulatory factors normally acting on the pituitary

Assessment of Target Gland Function If endocrine hypofunction is suspected, pituitary hormone deficiencies must be distinguished from primary failure of the thyroid, adrenals, or gonads Baseline laboratory studies should include: thyroid function tests (free T4) and determination of serum testosterone levels Testosterone is a sensitive indicator of hypopituitarism in women as well as in men

In primary target gland hypofunction, such as autoimmune polyglandular syndromes types 1 and 2 (APS 1 and 2), TSH, LH, FSH, or ACTH will be elevated Low or normal values for these pituitary hormones suggest hypothalamic-pituitary dysfunction