UA1 - Ong Partie 1 Flashcards
Rappel: Anatomie et histologie des glandes surrénaliennes
1) Où est situé la glande?
2) Quels sont les 2 principales parties de la glande et quels sont leurs zones respectifs
1) au dessus des reins
2) CORTEX: capsule + zone glomerulaire + zone fasiculaire
MÉDULLAIRE: zone réticulaire + médullaire
Nommes les hormones de l’adénohypophyse et
- les hormones hypothalamiques qui les régulent (inhibiteurs ou activateurs?)
- leur organe cible
- leur intermediaire hormonale s’il y a lieu
- GH - Growth Hormone (linear and organ growth)
- TSH - Thyroid Stimulating Hormone (thermogenesis metabolism)
- ACTH - Adrenocorticotropin (cell homeostasis and function)
- FSH et LH Follicule-Stimulating Hormone et Lutheinizing Hormone (spermatogenesis and ovulation)
- PRL - Prolactin (lactation)
(Voir table 37.1)
Quels sont les 3 types de stéroïdes surrénaliennes?
1- minéralocorticoides (aldostérone)
2- glucocorticoides (cortisol)
3 - androgènes (androstenedione être DHEA)
Combien de cycles retrouve-t-on dans un steroide?
4 cycles (A B C et D)
À partir de quoi sont synthétisés les stéroïdes surrénaliens?
Cholesterol
Voir figure 39-1
GLUCORTICOIDES
Quels sont les effets pharmacodynamiques des glucocorticoides?
Glucocorticoids INCREASE serum GLUCOSE LEVELS and thus STIMULATE INSULIN release (glycogen storage increases) and INHIBIT the UPTAKE of GLUCOSE by MUSCLE CELLS and ADIPOCYTES , while they STIMULATE HORMONE SENSITIVE LIPASE and thus lipolysis.
The NET RESULTS of these actions are most APPARENT IN the FASTING STATE , when
- the increase supply of glucose from gluconeogenesis,
- the release of AMINO ACIDS from muscle catabolism,
- the inhibition of peripheral glucose uptake, and
- the stimulation of lipolysis (more FATTY ACIDS )
all contribute to MAINTENANCE of an ADEQUATE GLUCOSE SUPPLY TO the BRAIN by INCREASING NEOGLUCOGENESIS IN LIVER (fatty acid + amino acids = glucose in liver -> diabetogenic effect)
Although GLUCOCORTICOIDS STIMULATE RNA and PROTEIN SYNTHESIS in the LIVER (a.k.a. more enzymes AND thus more enzyme activity) ,
they have CATABOLIC AND ANTI ANABOLIC effects in
- lymphoid and connective tissue (anti inflammatory effect),
- muscle (ATTENTION protein synthesis decreases in muscle but increases in liver!!! + decrease glucose utilization + insuline sensitivity)
- peripheral fat (decrease glucose utilization + insuline sensitivity + increase lipolysis), and
- skin (collagen breakdown).
SUPRAPHYSIOLOGIC AMOUNTS of GLUCOCORTICOIDS lead to
- decreased muscle mass and
- weakness and
- thinning of the skin.
CATABOLIC and antianabolic EFFECTS on BONE are the cause of OSTEOPOROSIS IN CUSHING’S SYNDROME and impose a major limitation in the long-term therapeutic use of glucocorticoids.
Other Effects
GLUCOCORTICOIDS have important EFFECTS on the NERVOUS SYSTEM .
Increased amounts of glucocorticoids often produce behavioral disturbances in humans: initially INSOMNIA and EUPHORIA and subsequently DEPRESSION .
GLUCORTICOIDES
Quel est l’effet principal des glucocorticoides
1) chez les enfants?
2) chez le foetus?
1) In CHILDREN , GLUCOCORTICOIDS REDUCE GROWTH . This effect may be partially prevented by administration of growth hormone in high doses, but this use of growth hormone is not recommended.
2) Glucocorticoids have IMPORTANT EFFECTS on the development of the FETAL LUNGS .
Indeed, the structural and functional changes in the lungs near term, including the PRODUCTION of PULMONARY SURFACE-ACTIVE MATERIAL required for air breathing (SURFACTANT ), are STIMULATED by GLUCOCORTICOIDS .
GLUCORTICOIDS
Quel est l’effet PRINCIPAL des glucocorticoides et comment réussissent-ils à faire cette effet?
Glucocorticoids dramatically REDUCE the MANIFESTATIONS of INFLAMMATION . This is due to their profound EFFECTS on the CONCENTRATION , DISTRIBUTION , and FUNCTION of PERIPHERAL LEUKOCYTES and to their SUPPRESSIVE EFFECTS on the INFLAMMATORY CYTOKINES and CHEMOKINES and on other mediators of inflammation
In ADDITION to their effects on leukocyte function, GLUCOCORTICOIDS influence the inflammatory response by REDUCING the PROSTAGLANDIN , LEUCOTRIENE, and PLATELET-ACTIVATING FACTOR SYNTHESIS that results from activation of phospholipase A2.
Finally, GLUCOCORTICOIDS REDUCE EXPRESSION of COX-2, the inducible form of this enzyme, in inflammatory cells, THUS REDUCING the AMOUNT of ENZYME AVAILABLE TO PRODUCE PROSTAGLANDIN.
GLUCOCORTICOIDS cause VASOCONSTRICTION when applied directly to the skin, possibly by suppressing mast cell degranulation. They also DECREASE CAPILLARY PERMEABILITY by reducing the amount of histamine released by basophils and mast cells. Et
GLUCOCORTICOIDES
Quelle est l’effet des glucocorticoides sur les autres hormones?
GLUCOCORTICOIDS given chronically SUPPRESS the pituitary RELEASE of
- ACTH,
- growth hormone,
- thyroid-stimulating hormone, and
- luteinizing hormone.
GLUCOCORTICOIDES
Comment les glucorticoides causent l’ostéoporose?
Large doses of glucocorticoids appear to ANTAGONIZE the EFFECT of VITAMIN D on CALCIUM ABSORPTION (plus inhibit release of GH)
GLUCOCORTICOIDS Quelle est l'effet des glucocorticoids 1) au niveau GI? 2) au niveau du gras? 3) au niveau hemato?
LARGE DOSES of glucocorticoids have been associated with
1) the development of PEPTIC ULCER , possibly by suppressing the local immune response against Helicobacter pylori.
2) They also promote FAT REDISTRIBUTION in the body, with INCREASE of VISCERAL , FACIAL , NUCHAL , and SUPRACLAVICULAR FAT
3) The glucocorticoids also have IMPORTANT EFFECTS on the HEMATOPOIETIC SYSTEM . In addition to their effects on leukocytes, they INCREASE the NUMBER of PLATELETS and RED BLOOD CELLS
GLUCOCORTICOIDS
Expliques la régulation de la sécrétion du cortisol.
In the NORMAL ADULT , in the ABSENCE of STRESS , 10–20 mg of cortisol is SECRETED DAILY . The rate of secretion follows a CIRCADIAN RHYTHM governed by pulses of ACTH that PEAK in the EARLY MORNING hours and AFTER MEALS , ESPECIALLY after LUNCH.
Rythme circadien ou Stress -> CRH -> ACTH -> stimulation des glandes surrénales -> cortisol
Cortisol: feed-back négatif sur adenohypophyse et sur hypothalamus
Au niveau des tissus périphérique:
1- cortisol convertie en cortisone (métabolite inactif) via HSD11B2*
2- cortisone convertie en cortisol vis HSD11B1
- HSD11B2: HydroxySteroid Dehydrogenase II
GLUCOCORTICOIDES
Comment est-ce que les glucocorticoides circulent dans le sang?
Corticosteroid-binding globulin (CBG), an α2 globulin synthesized by the liver, binds about 90% of the circulating hormone under normal circumstances.
The REMAINDER is FREE (about 5–10%) or LOOSELY BOUND to ALBUMIN (about 5%) and is AVAILABLE to exert its EFFECT on target cells.
MINÉRALOCORTICOIDES
Combien d’aldosterone est lié au protéines plasmatiques?
<50%
ANDROGÈNES
1) Comment circulent les androgènes?
2) comment est ce que les androgènes sont éliminés?
1) Liés au SHBG et à l’albumine
2) ils sont convertis en 17-ketosteroids et éliminés dans l’urine
GLUCOCORTICOIDES
Expliques leur mécanisme d’action
A model of the interaction of a steroid, S (eg, cortisol), and its receptor, R, and the subsequent events in a target cell. (Voir illustration p. 2 fiche Cushing)
The steroid is present in the blood in bound form on the CORTICOSTEROID-BINDING GLOBULIN (CBG) but enters the cell as the free molecule.
The INTRACELLULAR RECEPTOR is BOUND to STABILIZING PROTEINS , including two molecules of HEAT-SHOCK PROTEIN 90 (hsp90) and several others, denoted as “X” in the figure. This RECEPTOR COMPLEX is INCAPABLE of ACTIVATING TRANSCRIPTION .
When the COMPLEX BINDS a molecule of CORTISOL , an UNSTABLE COMPLEX is CREATED and the hsp90 and associated molecules ARE RELEASED .
The STEROID-RECEPTOR COMPLEX is now able to DIMERISE , ENTER the NUCLEUS , BIND to a GLUCOCORTICOID RESPONSE ELEMENT (GRE) ON the REGULATORY REGION of the GENE , and regulate transcription by RNA polymerase II and associated transcription factors.
A VARIETY of REGULATORY FACTORS (not shown) may participate in FACILITATING (coactivators) or INHIBITING (corepressors) the STEROID RESPONSE .
The resulting mRNA is EDITED and EXPORTED TO THE CYTOPLASM for the PRODUCTION of PROTEIN that brings about the final hormone response.
An ALTERNATIVE to the STEROID-RECEPTOR COMPLEX INTERACTION with a GRE IS an INTERACTION WITH AND ALTERING the FUNCTION of OTHER TRANSCRIPTION FACTORS, such as NF-κB in the nucleus of cells.
MINÉRALOCORTICOIDES
Qu’est-ce qui régule la sécrétion des minéralocorticoides?
Although aldosterone is no less than 1/3 as effective as cortisol in suppressing ACTH, the QUANTITIES of ALDOSTERONE PRODUCED by the ADRENAL CORTEX and its plasma concentrations ARE INSUFFICIENT to PARTICIPATE in any SIGNIFICANT FEEDBACK CONTROL of ACTH secretion.
WITHOUT ACTH, ALDOSTERONE secretion FALLS TO about HALF the normal rate, INDICATING that OTHER FACTORS , eg, ANGIOTENSIN , are able to MAINTAIN AND perhaps REGULATE its SECRETION (see Chapter 17).
Premièrement:
Appareil juxtaglomérulaire -> rénine -> transformation de l’angiotensinogène en ANG1 -> transformation de ANG1 en ANG2 -> sécrétion d’aldostérone -> rétention de Na et eau -> augmentation de TA -> augmentation de la pression de l’a. rénale
Deuxièmement:
Catecholamines ou macula densa peuvent affecter appareil juxtaglomérulaire
Troisièmement :
Aldosterone augmente l’excrétion de K
MINÉRALOCORTICOIDES
Dans quelle partie de la surrénale les minéralocorticoides sont synthétisés?
Aldosterone is SYNTHESIZED mainly in the ZONA GLOMERULOSA of the adrenal cortex
GLUCOCORTICOIDES
Les glucorticoides ont-ils ont un effet minéralocorticoides? Si oui, comment?
Some of the effects of glucocorticoids can be attributed to their binding to mineralocorticoid receptors (MRs). Indeed, MRs bind aldosterone and cortisol with similar affinity. A mineralocorticoid effect of cortisol is avoided in some tissues by expression of 11β-hydroxysteroid dehydrogenase type 2, the enzyme responsible for biotransformation to its 11-keto derivative (cortisone), which has minimal affinity for aldosterone receptors.
MINÉRALOCORTICOIDES
Quelle est le mécanisme d’action des minéralocorticoides?
Mineralocorticoids act by binding to the mineralocorticoid receptor in the cytoplasm of target cells, especially principal cells of the distal convoluted and collecting tubules of the kidney. The drug-receptor complex activates a series of events similar to those described above for the glucocorticoids and illustrated in Figure 39–4.
The major effect of activation of the aldosterone receptor is increased expression of Na+/K+-ATPase and the epithelial sodium channel (ENaC).
It is of interest that this RECEPTOR has the SA ME AFFINITY for CORTISOL , which is present in much higher concentrations in the extracellular fluid. The SPECIFICITY FOR MINERALOCORTICOIDS in the KIDNEY appears to be conferred, at least in part, by the presence of the enzyme 11β-hydroxysteroid dehydrogenase type 2, which converts cortisol to CORTISONE .
The latter has LOW AFFINITY for the RECEPTOR and is INACTIVE as a MINERALOCORTICOIDS or GLUCOCORTICOID in the KIDNEY .
ANDROGÈNES
1) Quels sont les androgènes principaux?
2) Ces androgènes sont-ils responsables des changement pubères?
1) The adrenal cortex secretes large amounts of DHEA ( and its sulfated form) and smaller amounts of androstenedione and testosterone + estradiol (<5%).
2) Although these androgens are thought to contribute to the normal maturation process, they do not stimulate or support major androgen-dependent pubertal changes in humans.
