Endocrinology and Reproductive Physiology

At the end of this unit, the student will be able to master the normal physiology of the endocrine glands and functions related to reproduction. Physiopathological situations are presented during the course and form an integral part of the subject. Once the subject has been acquired, the student must be able to reason about situations that could be found in a healthy person or in a patient.

For the section on reproductive physiology, the objectives are as follows:

CHAPTER 1: The Gonadotropic Axis and Sexual Steroids

1. Be able to describe the hypothalamo-pituitary axis.
2. Be able to explain the regulation of GnRH neurons by Kisspeptin neurons and KNDy neurons in the hypothalamus. Know the main factors that positively or negatively influence these regulatory mechanisms. Understand the importance of the pulsatile secretion of GnRH—see summary table.
3. Understand and explain the consequences of loss-of-function mutations in the KAL1 gene, loss-of-function mutations in the KISS1R gene, and gain-of-function mutations in the KISS1R gene.
4. Describe the mode and site of action of LH and FSH in males and females.
5. Be able to describe and compare the regulation of gonadal axis activity from fetal life through to the end of life in males and females.
6. Know the age ranges for the onset of puberty in boys and girls, as well as the criteria for precocious and delayed puberty.
7. Know the five major families of steroid hormones.
8. Explain and compare ovarian steroidogenesis and testicular steroidogenesis (see also Chapters 2 and 3).
9. Briefly describe steroid receptors and the transport mechanisms of steroids (see also Chapters 2 and 3).

CHAPTER 2: The Male Reproductive System

1. Name and describe the different functions of the Sertoli cell.
2. Understand and describe the role of the Leydig cell.
3. Describe testicular steroidogenesis and its regulatory mechanisms—see summary table.
4. Know the peripheral derivatives of testosterone, the enzymes involved in their conversion, and describe the potential benefit of 5-alpha-reductase inhibitors.
5. Know the actions of testosterone and its derivatives (dihydrotestosterone, estradiol)—see slides and summary table.
6. Briefly describe the modes of action (genomic and non-genomic), transport and metabolism of androgens.
7. Understand and explain the regulatory mechanisms of male gonadal function—see slides and summary table.
8. Describe the evolution of androgen secretion throughout life and the resulting consequences.

CHAPTER 3: The Female Reproductive System

1. Describe follicular development and its regulatory mechanisms. Understand and describe the functions of granulosa cells and theca interna cells.
2. Describe ovarian steroidogenesis and its regulatory mechanisms—see summary table.
3. Explain, using a diagram, the regulation of female gonadal function and the different phases of the menstrual cycle at both the ovarian and pituitary levels—see slide.
4. Briefly explain the effects of ovarian steroids on the endometrium and extra-genital organs.
5. Describe the evolution of ovarian steroid secretion throughout life and the resulting consequences.
6. Be able to define the terms adrenarche, thelarche, and menarche.
7. Explain the main symptoms of menopause.

CHAPTER 4: Disorders of Sexual Differentiation

1. Understand and describe the terms "genetic/chromosomal sex," "gonadal sex," and "phenotypic sex".
2. Know and understand the molecular regulatory scheme of sexual differentiation—see diagram.
3. Know the four main causes of DSD with sex chromosome abnormalities, and describe their clinical consequences—see slides and summary table:
4. DSD with ovotestis ("true hermaphroditism")
5. 45,X and Turner variants
6. 47,XXY and Klinefelter variants
7. 45,X/46,XY with mixed gonadal dysgenesis (MGD)
8. Know the two main causes of 46,XY DSD with gonadal dysgenesis and describe their clinical consequences—see slides and summary table:
9. SRY gene mutation or deletion (Swyer syndrome)
10. SOX9 gene mutation
11. Know the three main causes of 46,XY DSD with abnormal sexual differentiation and describe their clinical consequences—see slides and summary table:
12. Androgen insensitivity syndrome (complete and partial) + mode of inheritance
13. Testosterone deficiency (LH receptor mutation, Smith-Lemli-Opitz syndrome)
14. Dihydrotestosterone deficiency (5-alpha-reductase deficiency)
15. Know the two main causes of 46,XX DSD with gonadal dysgenesis and describe their clinical consequences—see slides and summary table:
16. SRY gene translocation onto the X chromosome
17. Duplication of SOX9 gene or regulatory sequences
18. Know the main causes of 46,XX DSD with androgen exposure and describe their clinical consequences—see slides and summary table:
19. Congenital adrenal hyperplasia
20. Maternal adrenal tumor, placental tumor
21. Exogenous androgen exposure
22. Aromatase deficiency
23. Understand the consequences of testicular regression syndrome—see slides and summary table.
24. Understand the consequences of interstitial deletion of the Y chromosome (AZFa, AZFb, AZFc regions)—see slides and summary table.
25. Understand the consequences of MIS (Müllerian Inhibiting Substance) deficiency—see slides and summary table.

CHAPTER 5: Physiological Aspects of Pregnancy, Parturition, Lactation

1. Describe the main characteristics and functions of beta-HCG.
2. Understand the concept of the feto-maternal-placental unit and its importance for steroidogenesis during pregnancy; describe the functions of placental progesterone and estrogens.
3. Know the functions of GH-V and hPL.
4. Understand and describe the functions of the placental barrier.
5. Describe maternal physiological changes during pregnancy: endocrine modifications, cardiovascular, respiratory, renal, and gastrointestinal systems.
6. Know the definition and main stages of parturition.
7. Describe the actions of the different factors regulating the stages of parturition (roles of progesterone, estrogens, prostaglandins, CRH, oxytocin). Illustrate their interactions with a diagram. Describe some factors involved in prematurity.
8. Describe the hormonal regulation of mammary gland development at different life stages.
9. Describe the main characteristics, regulation, and functions of prolactin. Understand the concept of lactational amenorrhea. Describe the symptoms and treatment of prolactinoma.