52: Introduction to Endocrinology Flashcards
Explain the cellular basis of peptide and steroid hormone actions, including differences in tissue specificity, receptors, onset of action, etc.
True hormones (endocrine secretions) are released by “ductless glands” and are carried by the bloodstream to their sites of action. They are part of a larger group of substances that includes autocrine, paracrine, and neuroendocrine secretions.
Hormones can be classified by their chemical composition: Hormones are typically blood borne polypeptides, amines or steroids that bind with high affinity to specific receptors.
Peptide and protein hormones activate receptors on the cell surface. Peptide hormones are typically stored in secretory vesicles. Peptide hormone receptors are in the cell membrane. Peptide hormones typically activate cytoplasmic signaling cascades.
Steroid hormones (and thyroid hormones) enter the cell and activate nuclear receptors (and sometimes cytoplasmic). Steroid hormones are typically produced on demand. Steroid hormone receptors are in the nucleus (or sometimes in the cytoplasm). Steroid hormones typically up-regulate or down-regulate transcription of genes.
Response times differ between peptide and steroid hormones.
Some hormones are released by cells and act locally in a paracrine or autocrine manner. Neuroendocrine hormones are secreted by neurons into the blood to influence the function of target cells.
Explain the importance of pulsatile and diurnal patterns of hormone secretion, and explain negative feedback regulation of hormonal secretion.
Hypothalamic and pituitary hormones are often released in a cyclical fashion that can be affected by the time of day as well as behavior
Typical variations in growth hormone (GH) secretion throughout the day demonstrate the especially powerful effect of strenuous exercise and also the high rate of GH secretion that occurs during the first few hours of deep sleep. GH secretion occurs during exercise.
Endocrine systems use positive and especially negative feedback to control the amounts of circulating hormones.
They are “closed-loop’ systems that can be simple or involve hierarchical control. In this manner, the system senses when it should increase or decrease its activity.
Peptides that feedback on the hypothalamic-pituitary axis are able to pass the blood-brain barrier.
Feedback of hormones released from peripheral glands onto the hypothalamic-pituitary axis is called long-loop feedback.
Short-loop feedback refers to anterior pituitary hormones feeding back on hypothalamus.
Negative and Positive Feedback Regulation:
In most cases, a hypothalamic- pituitary-target gland axis is regulated by negative feedback, whereby the trophic hormone of the anterior pituitary gland has negative feedback effects on the hypothalamus, and the target gland hormone has negative feedback effects on both the hypothalamus and the anterior pituitary.
Through these mechanisms, illustrated for the hypothalamus-pituitary-testes axis, levels of the target gland hormone are maintained within the normal physiological range.
In a few specific cases, positive feedback can also occur. For example, during the late follicular and ovulatory phases of the menstrual cycle, high levels of estradiol actually cause greater secretion of the hypothalamic releasing hormone and trophic hormones in that system, resulting in the surge in pituitary hormone release that is responsible for ovulation at midcycle.
Describe the cell origins, actions, and regulation of the posterior and anterior pituitary hormones, including vascular supply and general anatomical features of the pituitary gland.
Anterior pituitary is derived from the oral ectoderm = epithelial tissue
Posterior pituitary is derived from the neuroectoderm = neural tissue
The hypothalamic-pituitary axis exerts central control over multiple endocrine organs. The pituitary gland, also referred to as the hypophysis, is highly vascularized and lies at the base of brain in the sella turcica. Secretion of pituitary hormones is regulated by the hypothalamus via vascular (anterior) and neural (posterior) connections.
The anterior pituitary (adenohypophysis) and posterior pituitary (neurohypophysis) are derived from different embryonic tissues and function as separate glands. The posterior pituitary receives arterial blood.
The anterior pituitary receives venous blood carrying neuropeptides from the hypothalamus and pituitary stalk to different cell types in the gland. Anterior pituitary hormones are proteins and glycoproteins.
Axons from hypothalamic nuclei extend to the median eminence, where they release hormones into the hypophyseal portal circulation, which carries them directly to the anterior pituitary. At the anterior pituitary, these hormones inhibit or stimulate the release of various trophic hormones into the systemic blood.
Secretion of posterior pituitary hormones is regulated by the hypothalamus via neural connections. Axons from hypothalamic nuclei extend to the posterior pituitary, where hormones (oxytocin and vasopressin) are stored until released into the systemic bloodstream (oxytocin & vasopressin made in hypothalamus & stored in posterior pituitary). The posterior pituitary receives arterial blood. Posterior pituitary hormones are smaller molecular mass peptides that are associated with neurophysins.
Hypothalamic releasing factors are delivered to the anterior pituitary via a portal connection called the hypophyseal portal system.
Overview of Anterior Pituitary Function: The anterior pituitary gland is controlled by releasing and inhibitory hormones secreted into the hypophyseal portal circulation; these hormones reach the anterior pituitary directly through this portal circulation without entering the general circulation.
Under control of these factors, specific secretory cell types of the anterior pituitary secrete six major trophic hormones (TSH, ACTH, FSH, LH, prolactin, and GH), which act on distal endocrine glands. Trophic hormones and the target gland hormones have feedback effects on these endocrine systems, designed to regulate blood levels of the target gland hormone.
Explain the actions of hypothalamic factors that regulate pituitary hormone secretions, including their route of transport to the pituitary, and how they are regulated.
Releasing factors & hormones secreted by the anterior & posterior pituitary glands:
Anterior Pituitary:
Hypothalamic GnRH releases FSH (regulation of ovarian follicle development).
Hypothalamic GnRH releases LH (spermatogenesis, estrogen and androgen secretion).
Hypothalamic CRH releases ACTH (stimulation of adrenal cortex hormone secretion).
Hypothalamic TRH releases TSH (regulation of thyroid hormone secretion).
Prolactin (stimulation of milk secretion). Prolactin inhibited by dopamine. The release of most anterior pituitary hormones is controlled by hypothalamic releasing factors, except for prolactin.
Endorphins (endogenous opiates).
Hypothalamic GHRH releases GH also called somatotropin (growth of long bones). GH inhibited by somatostatin.
Posterior pituitary hormones are synthesized in large neuronal cell bodies in the hypothalamus (paraventricular & supraoptic), then transported down axons that terminate in the posterior pituitary gland, & stored in nerve terminals in the posterior pituitary gland until release into the bloodstream. Hormones stored in posterior pituitary:
AVP or vasopressin or ADH made in hypothalamus (increases BP—Vasopressin regulates the body’s retention of water by acting to increase water reabsorption in the collecting ducts of the kidney nephron & it constricts vessels).
Oxytocin is made in hypothalamus (stimulates uterine contractions)
Prolactin, unlike other anterior pituitary hormones, is under tonic inhibitory control by dopamine. Thus, circulating prolactin increases if the pituitary stalk is severed.
Prolactin is the major hormone that stimulates milk production during lactation. It also promotes breast development during puberty and pregnancy, and inhibits ovulation.
Unlike the other anterior pituitary hormones, prolactin is under tonic inhibitory control by dopamine (aka PRIF).
TRH (thyrotoprhic releasing hormone) stimulates prolactin release.
Prolactin exerts negative feedback on its own release by enhancing hypothalamic dopamine release via a short-loop pathway.
Circulating prolactin increases if the pituitary stalk is severed or an individual is taking a dopamine receptor antagonist (D2 type; e.g., certain antipsychotic agents).
Excessive prolactin secretion (hyperprolactinemia) is often treated with dopamine receptor agonists such as bromocriptine.
Oxytocin is a neuropeptide hormone that stimulates milk ejection (let-down) from the breasts in response to suckling, and uterine contractions during parturition in response to dilation of the cervix.
Oxytocin can also be secreted in response to sight, smell or sound of an infant; and orgasm.
The hypothalamic cell bodies that synthesize oxytocin are primarily in the paraventricular nuclei.
Antidiuretic hormone (ADH; also known as vasopressin) is synthesized mainly in the supraoptic nuclei (and also the paraventricular nuclei) of the hypothalamus and is stored and released at the posterior pituitary. Its main function is in water balance; it is released in response to increased osmolarity of extracellular fluid and decreased blood pressure and has the major effect of promoting water reabsorption by the kidney. When ADH levels in plasma are high, a low volume of concentrated urine is produced since water is being retained, thus making urine more concentrated.
ADH is a major regulator of body fluid osmolarity. Decreased body fluid osmolarity inhibits ADH secretion. Increased body fluid osmolarity stimulates ADH secretion–ADH secretion should decrease osmolarity because water concentration will increase.
When serum osmolality increases, ADH is released. This keeps water from leaving in the urine and increases the amount of water in the blood. And it helps restore serum osmolality to normal levels.
When you drink too much water, serum osmolality decreases. When serum osmolality decreases, ADH is suppressed. This increases the amount of water in your urine and prevents too much water from building up in your body (overhydration).
ADH secretion increases in response to an increase in serum osmolarity. For example, water deprivation leads to increased serum osmolarity which is ‘sensed’ by osmoreceptors in the hypothalamic neurons that synthesize ADH.
ADH acts specific cells/regions of the kidney to promote water reabsorption, thus decreasing body fluid osmolarity towards normal (homeostasis). This action involves a receptor called V2.
ADH (vasopressin) also causes contraction of vascular smooth muscle by stimulating a different receptor (V1). This leads to an increase in total peripheral resistance.
Failure of the posterior pituitary to secrete ADH is called central diabetes insipidus. Affected individuals produce large volumes of dilute urine, and their body fluids become concentrated. ADH deficiency results in decreased urine osmolality & increased serum osmolarity, hypernatremia (abnormally high concentration of plasma Na+), and polydipsia (frequent drinking due to extreme thirst).
Hypopituitarism refers to the inability of the pituitary gland to produce hormones or an insufficiency of hypothalamic-releasing hormones. The clinical symptoms are usually unspecific, but can be life threatening and lead to increased mortality. Patients with traumatic brain injury or subarachnoid hemorrhage are at high risk for hypopituitarism. Although pituitary tumors classically are the most common cause of hypopituitarism, new findings suggest that causes related to brain damage might outnumber pituitary adenomas in causing hypopituitarism. Treatment typically involves hormone replacement therapy.
