Physiology Female Hormones PDF 2024

Physiology of female hormones Author: Dr. Miguel Alejandro Dávalos Benítez Modified by: Dr. Yisel Guzmán Objectives Review synthesis of female hormones, including the role of granulosa and theca cells Understand female hormone regulations applying them in the changes in the ovarian and endometrial c...

Physiology of female hormones Author: Dr. Miguel Alejandro Dávalos Benítez Modified by: Dr. Yisel Guzmán Objectives Review synthesis of female hormones, including the role of granulosa and theca cells Understand female hormone regulations applying them in the changes in the ovarian and endometrial cycles Know the physiological effects of estrogens and progesterone Review the phases of the menstrual cycle Identify the hormonal changes throughout pregnancy, parturition, lactation and menopause. Synthesis and secretion of estrogen and progesterone Ovarian steroid hormones progesterone & 17β-estradiol STEROIDOGENESIS Hydroxysteroid oSynthesized by the ovarian follicles through the combined functions of the granulosa cells and the theca cells. oSame steps in the biosynthesis as those for the adrenal cortex and the testes. (Steroidogenesis) oAromatase is present in the ovaries which converts testosterone → 17β-estradiol (the major ovarian estrogen). LH stimulates cholesterol desmolase in the theca cells, the first step in the biosynthetic pathway. FSH stimulates aromatase in the granulosa cells, the last step in the synthesis of 17β-estradiol. 17βestradiol Progestins Prepare the uterus for pregnancy Prepare the breasts for lactation Estrogens Ovaries, Fallopian tubes, Vagina, Uterus Proliferation and growth Responsible for the development of secondary sexual characteristics Regulation of the ovaries Oogenesis and secretion of the female sex steroid hormones are controlled by the hypothalamicpituitary axis. 1.- Act on the ovaries to stimulate follicular development and ovulation 2.- Stimulate the synthesis of the female sex steroid hormones. FSH Facts 1.- The granulosa cells are the only ovarian cells with FSH receptors. 2.- Stimulate estradiol synthesis. 3.- Stimulate the growth of granulosa cells in primary follicles. 4.- The locally produced estradiol supports the trophic effect of FSH on follicular cells. LH Facts 1.- Ovulation is initiated by LH. 2.- Stimulates formation of the corpus luteum. 3.- Maintains steroid hormone production by the corpus luteum during the luteal phase. In females, the hypothalamic-pituitary axis is controlled by both negative and positive feedback, depending on the phase of the menstrual cycle #feedbackpatternreverseal o Inhibin: produced by ovarian granulosa cells, and corpus luteum. As in the testes, it inhibits FSH secretion from the anterior pituitary. o Activin: also produced by ovarian granulosa cells, it stimulates FSH secretion from the anterior pituitary. o Mittelschmerz (“middle hurts”)—pain with ovulation. Pulsatile and cyclic secretion Actions of estrogen Female hormone effects Female hormone effects Uterus Fallopian tubes Estrogen → cell proliferation, growth, and increased contractility. Progesterone → increases secretory activity and decreases contractility. Estrogen → stimulates ciliary activity and contractility, aiding in the movement of sperm toward the uterus. Progesterone → increases secretory activity and decreases contractility. Vagina Estrogen → stimulates proliferation of epithelial cells. Progesterone → stimulates differentiation but inhibits proliferation of epithelial cells. Breast At puberty, with the onset of estrogen secretion, the lobular ducts grow and the area around the nipple, the areola, enlarges. Estrogen also increases the amount of adipose tissue → characteristic female shape. Progesterone collaborates with estrogen by stimulating secretory activity in the mammary ducts. Menstrual cycle Follicular (proliferative) phase: ▪ Dominated by 17β-Estradiol. ▪ Stimulates growth of the endometrium, growth of glands and stroma, and elongation of the spiral arteries, which supply the endometrium. ▪ Cervical mucus become copious, watery, and elastic. Luteal (secretory) phase: ▪ Dominated by progesterone. ▪ Uterine glands become more tortuous, accumulate glycogen in vacuoles, and increase their mucus secretions. ▪ The spiral arteries elongate more and become coiled. ▪ Decreases the quantity of cervical mucus. Follicular phase: 4-14 day. o Dominant follicle. o LH and FSH upregulate receptors = estradiol. o Proliferation of endometrium o Negative feedback to GnRH Ovulation phase: 14 day prior menses. o Burst of estradiol = positive feedback to GnRH → FSH/LH → ovulation. o Cervical mucus penetrable by sperm. o Estradiol decrese just after ovulation. Luteal phase: 14-28 days. o Corpus luteum -> progesterone (secretory activity of the endometrium and increase its vascularity, basal body temp increases, cervical mucus thicker) and estrogen receptor decreases. o Without fecundation -> regress of corpus luteum -> lowering of estradiol and progesterone. Menses: days 0-4/5 of the next MC. o Abrupt loss of estradiol and progesterone causes the endometrial lining and blood to be sloughed. o Primory follicles for the next cycle are being recruited. Early pregnancy 1. 2. 3. Fertilization: 24 hours after ovulation → in the ampulla → blastocyst. Implantation: 5 days after ovulation, the blastocyst has an inner mass of cells → fetus, and an outer rim of cells → trophoblast. Dependent on a low estrogen/progesterone ratio, under stimulation by progesterone, the endometrium differentiates into a specialized layer of decidual cells. The trophoblast begins secreting HCG: it “informs” the corpus luteum that fertilization has occurred → continues progesterone and estrogen production (approximately 8 days after ovulation). Pregnancy The highest levels of estrogen and progesterone occur during pregnancy. Early – corpus luteum Later - placenta Estrogen: stimulates growth of the myometrium, growth of the ductal system of the breasts, prolactin secretion, and enlargement of the external genitalia. Progesterone: maintains the endometrial lining of the uterus and increases the uterine threshold to contractile stimuli. 1st trimester o HCG produced by trophoblast (8 days of fertilization) → stimulates corpus luteal production of progesterone and estrogen. o Maximal at approximately gestational week 9 and then decline. 2nd and 3rd trimesters o The placenta → assumes responsibility for production of steroid hormones. o Progesterone → tranformed from cholesterol in the placenta. o Estriol → cholesterol to pregnenolone in the placenta → fetal circulation → DHEA sulfate (fetal adrenal cortex) then is hydroxylated by the liver → 16-OH DHEAsulfate → placenta (sulfate enzyme + aromatase) → estriol. Aromatase converts testosterone into estradiol and androstenedione, which is then transformed into estrone. Potency: estradiol > estrone > estriol. Ovary (17β-estradiol) Placenta (estriol) Adipose tissue (estrone) Prolactin Prolactin is pro-lactation Hormones during parturition Near term, the fetal hypothalamic-pituitaryadrenal axis is activated and the fetal adrenal cortex produces → cortisol→ increases the estrogen/progesterone ratio → increases the sensitivity of the uterus to contractile stimuli. Estrogen stimulates local production of the prostaglandins PGE2 and PGF2α, they: ○ ○ ○ Increase the intracellular calcium concentration of uterine smooth muscle → increasing its contractility. Promote gap junction formation between uterine smooth muscle cells → synchronous contraction of the uterus. Cause softening, thinning, and dilation of the cervix early in labor. Hormones during parturition Oxytocin: Dilation of the cervix → stimulates oxytocin secretion. Uterine oxytocin receptors are up-regulated toward the end of gestation. Oxytocin is a powerful stimulant of uterine contractions. After delivery of the placenta, hormone concentrations return to their prepregnant levels, except for prolactin, whose levels remain high if the mother breast-feeds the infant Although prolactin levels are high (secretion stimulated by estrogens) during pregnancy, lactation does not occur because estrogen and progesterone block the action of prolactin on the breast → their inhibitory effects are removed after birth and lactation can proceed. Lactation is maintained by suckling, which stimulates the secretion of both oxytocin and prolactin. As long as lactation continues, there is suppression of ovulation because prolactin inhibits GnRH secretion and secundary the FSH and LH secretion. Menopause Is the cessation of menstrual cycles in women, and it occurs at approximately 50 years of age. The number of functioning ovarian follicles decreases → accordingly, estrogen secretion gradually declines and eventually ceases → reduced negative feedback on the anterior pituitary → higher levels of LH and FSH. Symptoms: thinning of the vaginal epithelium, decreased vaginal secretions, decreased breast mass, accelerated bone loss, vascular instability, and emotional lability. Obese women tend to be less symptomatic than nonobese women. HAVOCS Hot flashes (most common) Atrophy of the Vagina Osteoporosis Coronary artery disease Sleep disturbances References Linda S. Costanzo (2018), 6th edition. Physiology, chapter 10, pages 470 - 482. Guyton, A., Hall, J. (2016). Textbook of Medical Physiology. (14th Ed.). Philadelphia: ElsevierSaunders. Chapter 82. Pages 1027-1044