Reproductive physiology Sex hormones: Androgens Estrogens Gestagens Learning objectives 86 (also 90) Sex Genetic sex Gonadal sex Phenotypic sex XY - XX chromosomes testes - ovaries external features Tha female fetus develops without the need for ovarian hormones, and the female phenotype develops spontaneously, by default. The female reproductive system Myometrium The functional unit of the ovary is the follicle. 1
Embryology 4 million primordial follicles birth: 2 million puberty: 300 000 300-400 follicles reach maturity Menopause: decline in the number of primordial follicles, the cycles disappear Puberty Beginning: 7-13/9-15 years in girls/boys Over a period of 3-4 years or longer Hormonal changes: Adrenarche Pulses of Gonadotropin-releasing hormone (GnRH) Secretion of LH and FSH Secretion of sex hormones Sex hormones induce somatic changes Growth spurt Secondary sex characteristics -Pubarche: growth of axillary and pubic hair -Thelarche: development of breast -Menarche: first menstruation girls Mental changes 2
Puberty has been starting earlier and earlier since the beginning of the Industrial Revolution in the 19th century in the Western world (Acceleration). Improved civic sanitation Improved lighting Improved nutrition (menarche - 47 kg body weight) Puberty is linked to the switching on of hypothalamic GnRH neurons (Leptin?) 3
Activated KISS gene (arcuate nucleus) Kisspeptin (54 as) GPR-54 receptor GnRH PUBERTY IN 2013 Unravelling the mystery of puberty Ojeda, S. R. & Lomniczi, A. Nat. Rev. Endocrinol. 10, 67 69 (2014); HERSHEY'S KISSES (Pennsylvania, USA) Luteal phase Ovarian cycle 28 days Follicular phase 14 days Ovulation Luteal phase 14 days Theca cells Follicular phase 4
CORPUS LUTEUM CORPUS ALBICANS Ovarian hormones Steroids: - - -(Androgens) Estrogens: Estrone,, Estriol Gestagens:, 17-OH- Peptides: -Inhibin -Relaxin Steroid hormone biosynthesis Desmolase Cholesterol 17-OH-ase 17,20-lyase 17-HSDH Pregnenolone 17-OH-pregnenolone Androstanedione 3-HSDH 17-OH- Androstenedione Testosterone 21-OH-ase 11-OH-ase 11-deoxycorticosterone Corticosterone 11-deoxycortisol Cortisol aromatase Estrone 18-OH-ase 18-HSDH 18-OH-costicosterone Aldosterone LIVER Estriol DHEA = Dehydroepiandrosterone days 5
Interactions between theca and granulosa cells LH FSH CIRCULATION THECA CELLS GRANULOSA CELLS ANTRUM androstenedione androstenedione Follicular phase LH LH CIRCULATION androstenedione androstenedione Luteal phase 6
Transport Free: 2 % 2 % Bound to protein: -Albumin 60 % 50 % -Gonadal steroid-binding globulin 38 % - Corticosteroid-binding globulin 48 % Receptors: Intracellular receptors (membrane receptors) PHYSIOLOGICAL EFFECTS OF OVARIAN STEROID HORMONS ESTRADIOL Ovary: ovum maturation Oviduct: increases motility Uterus -Cervix: increases mucus secretion -Endometrium: proliferatory phase -Myometrium: increases membrane excitability and number of oxytocin receptors Mammary gland: growth of ducts Bone: mineral deposition Increases HDL:LDL - anti-atherosclerotic effect Hepatic protein synthesis: transport proteins, clotting factors PROGESTERONE Uterus -Cervix: increases mucus consistency -Endometrium: secretory phase -Myometrium: hyperpolarization Mammary glands: lobular-alveolar development General body effect: rise in basal metabolic rate (ANDROGENS) CNS: libido Skin: growth of hair 7
Luteinizing hormone (LH) Follicle-stimulating hormone (FSH) Estrogens Basal body temperature OVARY ENDOMETRIUM Loss of blood: 30-50 ml Loss of iron: 15 mg bleeding THE MENSTRUAL CYCLE Ovulation days Hypothalamus-anterior pituitary-ovary central nervous system GnRH: Gonadotropin releasing hormone FSH: Follicle-stimulating hormone LH: Luteinizing hormone Adenohypophysis + Inhibin: inhibits the production of GnRH and FSH effects effects Positive feedback: high concentration increases the number of GnRH receptors on the LH/FSH secreting cells in the adenhypophysis. 8
Oral contraception Oral contraceptives are chemicals taken by mouth to inhibit normal fertility. Inhibition of the ovulation Increased mucus consistency in cervix Thin endometrial layer Cessation of ovarian cycles - Menopause - Pregnancy Menopause: decline in the number of primordial follicles and are not secreted in the ovaries Atrophic changes in sex organs Slight masculinisation Secretion of GnRH Osteoporosis Secretion of FSH and LH hot flushes 9