The hypothalamo-pituitary-adrenal axis (HPAA) and the female hypothalamo-pituitary-gonadal axis (HPGA).

MECHANISMS OF CONTROL OF HORMONES

1.To Maintain homeostasis: insulin and glucagon maintain a constant level of glucose in the blood; 2. To Respond to a variety of external stimuli: catecholamines; 3. To follow various cyclical and development programs : sex hormones regulate the differentiation, sexual maturation, the menstrual cycle and pregnancy. The human endocrine system produces a large variety of hormones that enable the body :

Regulation of energy production (insulin, glucagon) Response to noxious stimuli (catecholamines, steroids) Regulation of growth (growth hormone) Regulation of reproductive and sexual function (steroids) Regulation of extracellular fluid and osmolarity (aldosterone, antidiuretic hormone) Control of metabolism Ca eP (calcitonin, Vit. D) Regulating growth, reproduction and cell differentiation (growth factors, oncogenes) HORMONES: Functions

STEROID HORMONES The biosynthesis of steroid hormones begins from cholesterol The main organs involved are the gonads, the adrenal cortex and the placenta In general, these hormones control metabolism regulating the expression of particular genes

STEROID HORMONES The main classes are: 1. Progestin (progesterone) (21C): they regulate the progress of pregnancy and are the precursors of all the steroid hormones 2. Glucocorticoids (cortisol and corticosterone) (21C): they act on carbohydrate metabolism, promoting gluconeogenesis. In pharmacological doses they abolish inflammatory reactions 3. Mineralocorticoids (aldosterone) (21C): they regulate the concentration of electrolytes in the blood, promoting the reabsorption of Na +, Cl-, HCO3-

4. Androgen (androstenedione, testosterone) (19C): they promote the development of male sex 5. Estrogens (estrone, estradiol) (18K): sex hormones that induce the female sexual characteristics Steroid hormones, in contrast to those peptide, are not stored in the reserve tissues, but they are producted where necessary and readily liberated in the plasma. The level of circulating hormone is regulated by the rate of synthesis

STEROID HORMONES Glucocorticoid and mineralocorticoid are synthesized in the adrenal cortex Androgens and estrogens are synthesized respectively in testis and ovary All steroid hormones act via nuclear receptors and they modify the expression of specific genes Androgens produced in the early stages of embryonic development drive the development versus the male fetus; low levels after birth until adolescence, then Testosterone increases for sperm production and maturation of the penis and testicles.

REGULATION OF TESTOSTERONE PRODUCTION

Regulation of gonadotropin secretion: The secretion of FSH and LH is stimulated by hypothalamic GnRH (gonadotropin releasing hormone), while it is affected partly by circulating levels of sex hormones (testosterone in men, estrogen and progesterone in females), with a feedback mechanism. Variable levels of FSH and LH are responsible for the menstrual cycle in women. FSH action: In male, FSH acts on the testis and, in particular, on some supporting cells (Sertoli cells) where the sperm develop In female the main role of FSH is to allow the maturation of ovarian follicles during the first part of the menstrual cycle and the production of estrogen by the ovary. LH action: In male, LH acts on the Leydig cells of the testes, responsible for producing testosterone. In female, LH is able to induce ovulation and to facilitate the production of progesterone by the corpus luteum (ie the residue of the ovarian follicle after the expulsion of the egg cell). Functions of gonadotropins (FSH and LH)

HORMONES AND CYCLE OF WOMAN

Hypothalamic–pituitary–adrenal (HPA) axis during pregnancy.

Hydrosoluble hormones PEPTIDE HORMONES Insulin (pancreas) Glucagon (pancreas) PTH (Parathyroid) Prolactin (Adenohypophysis) Oxytocin (hypothalamus) Vasopressin (Hypothalamic NOT PEPTIDE HORMONES Adrenaline and noradrenaline (medullary adrenal) Hormones of hydrophobic nature (protein, peptide, epinephrine, norepinephrine) circulate in free form in the blood

LIPOSOLUBLE HORMONES Adrenal cortex  cortisol  aldosterone  corticosterone Sex hormones androgens (testicles) estrogen (ovary) Hormones of hydrophobic nature (steroid-diidrossicalciferolo 1.25) are carried in the blood by binding specific proteins

Alberts et al., L’ESSENZIALE DI BIOLOGIA MOLECOLARE DELLA CELLULA, Zanichelli editore S.p.A. Copyright © 2005 STAGES OF CELL SIGNALING 1.Receptor activation The signal molecule binds to the receptor 2.Signal transduction The activated receptor stimulates a sequence of changes in the pathway of signal transduction 3.Cellular response Many different responses  Modification of the activity of one or more enzymes  Modification of the functions of a structural protein  Changes in gene expression

Hydrosoluble hormonessi They bind to receptors on the cell membrane and exert their effect mainly on metabolic activity through a second messenger The liposoluble hormones They bind to intracellular receptors and exert their effect mainly on the transcription of some genes The effect of hormones on target cells is achieved by interaction with specific receptors