Module 8

Describe the mechanism whereby which tacrolimus suppresses the immune system.

Tacromilus binds to immunophilin, which causes the proteins that are responsible for the inactive conformation of glucocorticoid receptors to dissociate from the receptors, thereby converting the receptors to their active forms. This causes down regulation of inflammatory cytokines and COX-2, decreased production of collagen, and interactions with transcription factors for the immune system.

Which of the following pharmacological agents can be used to treat Grave's disease? a) Clomiphene b) Carbimazole c) Bromocriptine d) Octreotide

b) Carbimazole

Which of the following main endocrine glands is considered to be the link between the nervous system and the endocrine system? a) Adrenal gland b) Hypothalamus c) Anterior pituitary d) Posterior pituitary

b) Hypothalamus

Excess growth hormone as the result of a benign pituitary tumor results in enlarged facial structures clinically referred to as acromegaly. Which of the following pharmacological approaches could be used to treat this condition? a) Administer a compound that enhances the release of growth hormone b) Reduce the metabolism and excretion of growth hormone with a small molecule c) Enhance the activation of circulating growth hormone in the periphery d) Provide competition at the receptor target with the use of an antagonist

d) Provide competition at the receptor target with the use of an antagonist

T/F Glucocorticoids influenced by adrenocorticotrophic hormone from the anterior pituitary are stored in the adrenal gland.

False

T/F Peptides synthesized in the hypothalamus are stored in the anterior pituitary gland.

False

T/F Raloxifene, a selective estrogen receptor modulator used for the prevention and treatment of postmenopause osteoporosis is both an antagonist and an agonist.

True

T/F The main mineralcorticoid is aldosterone.

True

T/F Thyroid hormones are classified as amine hormones.

True

Steroid hormones include all of the following except? a) Glucocorticoids b) Aldosterone c) Prolactin d) Androgens

c) Prolactin

What two characteristics distinguish hormones from neurotransmitters?

Both hormones and neurotransmitters are chemical messengers in the body. However, hormones are apart of the endocrine system and circulate systemically to produce effects on cells that are far away. On the other hand, neurotransmitters are a part of the nervous system and are released from the axon terminal into the synapse and act on the receptors of the next neuron.

Why is breastfeeding considered to be a natural contraceptive?

Breastfeeding is considered to be a natural contraceptive because prolactin that is stimulated to be released during suckling inhibits the release and response to gonadotrophin, which blocks the effect of gonadotrophin on the ovaries inhibiting ovulation.

Explain the mechanism whereby which Clomiphene induces ovulation?

Clominphene competes with natural estrogens in target receptors, which inhibits estrogen binding in the anterior pituitary and in the hypothalamus. Thus, clominphene prevents negative feedback and acutely increases secretion of GnRH, also stimulating FSH and LH secretion. The release of these hormones stimulates ovulation, and development of the corpus luteum.

T/F Both the luetinizing hormone (LH) and follicle-stimulating hormone (FSH) are secreted from the posterior pituitary gland.

False

T/F Atosiban is used to delay premature labor based on its ability to block β2 adrenergic receptors.

False Atosiban does not block β2 adrenergic receptors. Atosiban blocks oxytocin receptors. Oxytocin plays a role in birthing by causing regular coordinated uterine contractions leading to parturition. Therefore, oxytocin can be used to induce labor and conversely antagonizing oxytocin receptors can delay labor in the event of preterm labor.

T/F The administration of sildenafil leads to the activation of guanylate cyclase.

False Sildenafil inhibits phosphodiesterase type V. Originally intended as an anti-hypertensive agent, Sildenafil surprisingly produced a side effect in men that resulted in the commercialization of Sildenafil as an erectile dysfunction pharmaceutical. Phosphodiesterase inactivas cyclic GMP. Cyclic GMP is elevated in vascular smooth muscle as a result of nitric oxide activating soluble guanylyl cyclase. The result is vasodilation. Inhibition of phosphodiesterase maintains the elevated levels of cyclic GMP promoting vasodilation.

T/F Dehydroepiandrosterone or DHEA is an androgen precursor produced in the adrenal gland.

True

T/F Dopamine inhibits prolactin secretion.

True

T/F The precursor to both testosterone and glucocorticoids is cholesterol.

True

T/F Prolonged or chronic administration of a glucocorticoid such as prednisone has many adverse effects including increased abdominal fat and thinned skin.

True Prolonged administration of a glucocorticoid results in a variety of unwanted side effects similar to symptoms experienced by individuals with Cushing's syndrome. This unwanted side effects include increased abdominal fat, thinning of skin, easy bruising, poor wound healing, moon face, and muscle wasting to name a few.

Thyroid stimulating hormone enhances the generation of H2O2 in the thyroid gland, which in turn stimulates the production of T3 and T4. Discuss the significance of H2O2 in the process of thyroid hormone production.

Tyrosine iodination is required to produce the thyroid hormones T3 and T4. This iodination is catalyzed by the enzyme thyroperoxidase. However, thyroperoxidase requires H2O2 as an oxidizing agent (cofactor). Therefore, without H2O2, there would likely be hypothyroidism issues.

Which of the following compounds inhibits the iodination of tyrosine residues of thyroglobulin? a) Carbimazole b) Protirelin c) Liothyronine d) Hydrogen peroxide

a) Carbimazole

Metyrapone inhibits the enzyme 11-β-hydroxylase and thus inhibits the synthesis of a) Corticosterone and hydrocortisone b) Hydrocortisone c) Progesterone d) Corticosterone

a) Corticosterone and hydrocortisone Metyrapone can be utilized to treat Cushing's syndrome, a disorder associated with an excess of glucocorticoids. Metyrapone exerts its effect on the enzyme 11-β-hydroxylase, blocking the synthesis of both corticosterone and hydrocortisone.

5α-reductase inhibitors used for the treatment of benign prostatic hypertrophy include which of the following? a) Finasteride b) Raloxifene c) Anastrazole d) Flutamide

a) Finasteride Finasteride blocks the enzyme 5α-reductase, which is responsible for the conversion of testosterone to the active metabolite dihydrotestosterone. Prostatic hypertrophy is a condition in which the prostate becomes enlarged believed to be due to a change in the balance of hormones associated with age. Therefore, adjusting testosterone levels by inhibiting the enzyme responsible for testosterone synthesis is one clinical treatment for prostatic hypertrophy.

Breastfeeding is considered to be a natural contraceptive because prolactin that is stimulated to be released during suckling inhibits the release and response to which of the following? a) Gonadotrophin b) Protirelin c) Oxytocin d) Estradiol

a) Gonadotrophin Prolactin is secreted from the anterior pituitary at elevated levels during pregnancy. The main role of prolactin in women is the regulation of milk production. Thus, prolactin, along with other hormones, is responsible for the proliferation and differentiation of mammary tissue. During birth, prolactin levels spike initiating lactation. After birth, the stimulus for the increase of prolactin blood levels is suckling. Other than controlling milk production, prolactin also inhibits the release and response of gonadotrophin. Specifically, prolactin blocks the effect of gonadotrophin on the ovaries inhibiting ovulation. Therefore, breastfeeding can be deemed as a natural contraceptive as a result of stimulating prolactin secretion that inhibits gonadotrophin.

In the combination estrogen-progestogen contraceptive pill, the estrogen component acts primarily by inhibiting a) Secretion of FSH b) Ovulation c) Secretion of LH d)Mucus secretion

a) Secretion of FSH Follicle stimulating hormone (FSH) release from the anterior pituitary is inhibited by estrogen. In the absence of FSH, follicles containing an ovum don't mature. The progestogen component of the combination contraceptive pill inhibits the secretion of luteinizing hormone from the adrenal gland, which prevents ovulation and the secretion of mucus.

Which of the following is the name of recombinant growth hormone? a) Somatropin b) Somatorelin c) Sermorelin d) Somatostatin

a) Somatropin

Which of the following statements is true about Addison's disease? a) Symptoms include hypertension, poor wound healing and moon face b) An excess of ACTH is a contributing factor to the hyperpigmentation noted c) Arises due to an excess of glucocorticoids d) Pharmacological approach includes the administration of ketoconazole

b) An excess of ACTH is a contributing factor to the hyperpigmentation noted

Which of the following is a contraindication for taking combined estrogen and progesterone oral contraceptives that utilize a second generation progesterone? a) Deep vein thrombosis b) Concurrent administration of amoxicillin and deep vein thrombosis c) Diabetes mellitus type I d) Concurrent administration of amoxicillin

b) Concurrent administration of amoxicillin and deep vein thrombosis

Postpartum hemorrhage can be treated by which of the following? a) Estrogen b) Ergometrine c) Progestogen d) Ritodrine

b) Ergometrine Ergometrine, derived from the fungus Ergot, was identified as the compound responsible for abortions associated with Ergot-poisoning. This effect is due to the oxytocic principle able to induce strong contractions in a fully relaxed uterus. Ergometrine is also a moderate vasoconstrictor. Together these two effects reducing bleeding indicative of postpartum.

Insulin-like growth factor-1 also denoted as somatomedin provides a type of negative feedback inhibition of which of the following? a) Prolactin b) Growth hormone c) Corticotrophin d) Melanocyte-stimulating hormone

b) Growth hormone Insulin-like growth factor-1 release from the liver upon stimulation by growth hormone inhibits further release of growth hormone from the anterior pituitary. Prolactin secretion is negatively inhibited by dopamine. Corticotrophin or ACTH inhibits the release of corticotrophin releasing factor from the hypothalamus, which subsequently inhibits the release of corticotrophin itself.

Which of the following is NOT one of the naturally occurring estrogens found in females? a) Oestradiol b) Norethisterone c) Oestrone d) Oestriol

b) Norethisterone

Which of the following statements is true regarding Cushing's disease? a) Symptoms include low blood pressure and hypoglycemia b) Result of excess glucocorticoids c) Yields an excess action of renin-angiotensin system d) Consequence of the destruction of the adrenal gland

b) Result of excess glucocorticoids

Fludrocortisone can be antagonized by what compound? a) Metyrapone b) Spironolactone c) Aldosterone d) Ketoconazole

b) Spironolactone Spironolactone was discussed in module 6 as a pharmacological agent available for the treatment of hypertension. Mechanistically, spironolactone is an aldosterone antagonist. The effects of fludrocortisone can be inhibited by spironolactone, because fludocortisone is a synthetic mineralcorticoid having similar effects as the endgeonous minderalcorticoid, aldosterone.

Antiandrogens are therapeutically used for all of the following EXCEPT: a) To treat masculination in women b) To treat hypersexuality in male sex offenders c) Compensate for short stature associated with Turner's syndrome d) Adjunct treatment for prostate cancer

c) Compensate for short stature associated with Turner's syndrome

Glucocorticoids are used clinically for all of the following conditions EXCEPT: a) Asthma b) Hormone replacement therapy for Addison's disease c) Diabetes d) Eczema

c) Diabetes

Which of the following best describes octreotide? a) Short-acting analogue of somatostatin b) Short-acting analogue of somatotrophin c) Long-acting analogue of somatostatin d) Long-acting analogue of somatotrophin

c) Long-acting analogue of somatostatin Somatostatin is a hypothalamic hormone that inhibits the release of growth hormone from the anterior pituitary. Octreotide is a long-acting analogue of somatostatin. Somatotrophin, on the other hand, is another name for growth hormone.

Which of the following primarily stimulates progesterone secreted from the corpus luteum? a) Follicle-stimulating hormone b) Estrogen c) Luteinizing hormone d) Prolactin

c) Luteinizing hormone High concentrations of estrogen sensitize luteinizing hormone releasing cells of the anterior pituitary to gonadotrophin releasing hormone causing a mid cycle surge of luteinizing hormone. As a result the Graafian follicule swells rapidly and ruptures yielding ovulation. The remains of the Graafian follicule develop into the corpus luteum which secretes progesterone.

Which of the following statements best explains why metyrapone can be used in the diagnosis of the etiology of elevated serum ACTH? a) It directly blocks the synthesis of cortisol by inhibition of 21-β-hydroxylase (CYP21), which promotes increased ACTH formation from the anterior pituitary but not from ectopic sources b) It selectively decreases ACTH formation in pituitary adenomas and has no effect on ectopic production c) It acts at the anterior pituitary to increase the processing of ACTH from its precursor protein but has not effect on ACTH from ectopic sources d) It directly bocks the synthesis of cortisol by inhibition of 11β-hydroxylase (CYP1B1), which promotes increased ACTH formation from the anterior pituitary but not from ectopic sources

d) It directly bocks the synthesis of cortisol by inhibition of 11β-hydroxylase (CYP1B1), which promotes increased ACTH formation from the anterior pituitary but not from ectopic sources

Uterine contraction is stimulated by a) Atusiban b) Ritodrine c) Danazol d) Oxytocin

d) Oxytocin

Of the following statements, which is NOT true of melanocortins? a) Include the peptide hormones α-MSH, β-MSH, and γ-MSH b) Derived from the same precursor as adrenocorticotrophic hormone (ACTH) c) Play a role in the stimulation of melanin in skin and hair cells d) Produce effect upon binding to intracellular nuclear receptors

d) Produce effect upon binding to intracellular nuclear receptors