TR

Notes on Endocrine Control of Sex and Reproduction

Learning Objectives

  • Revise the function of the hypothalamus/pituitary/gonad (HPG) axis.

  • Understand how hormones sculpt internal and external sexual development before and after birth.

  • Understand how the initial choice between ovary and testis development is made during fetal development.

Endocrine Signaling Types

  • Endocrine: Long distance signaling via the bloodstream.

  • Paracrine: Short-range signaling; one cell communicates with neighboring cells.

  • Autocrine: Self-signaling; a cell expresses a signaling molecule and the receptor for that molecule.

  • A hormone may have all 3 functions

Hormonal Pathways

  • Main Reproductive Hormones:

    • Hypothalamus: GnRH (gonadotropin-releasing hormone).

    • Anterior Pituitary Gland: LH (luteinizing hormone), FSH (follicle-stimulating hormone).

    • Gonads: Produce oestrogens and androgens. Progesterone, inhibit, activin

    • Effects on Placenta: Production of hCG (chorionic gonadotropin), progesterone, hPL (placental lactogen).

Mechanism of Hormone Action

  • Hormones primarily exert effects by binding to specific receptors on or in target cells.

  • Nuclear Hormone Receptors (NHRs):

    • Steroid hormones bind to receptors in the cytoplasm and the complex enters the nucleus to activate gene transcription. All sex steroids act via specific NHRs(e.g ER, PR, AR

Sex Determination and Development

  • The embryonic development stage before 6 weeks gestation features undifferentiated gonads capable of becoming either ovaries or testes.

  • Genetic sex determination influences male or female pathway development:

    • Male differentiation is generally driven by hormonal signals including testosterone and AMH (Anti-Müllerian Hormone).

Key Hormones and their Functions

  • Testosterone (T):

    • A steroid hormone synthesized from cholesterol, with much higher levels in males.

    • Functions include promoting male secondary sexual characteristics via conversion to DHT (dihydrotestosterone).

  • Anti-Müllerian Hormone (AMH):

    • Inhibits the development of the Mullerian duct in males, preventing female reproductive structure formation.

Differences Between Males and Females

  • Key differences influenced by hormone levels:

    • Size, muscularity, fat distribution, aggression, voice depth, and balding patterns are affected by testosterone levels.

    • Castration before puberty alters these characteristics and indicates testosterone's role in developing the male phenotype.

    • 1849- Arnold Berthold proves that transplanted testes alter chicken physiology-one of the founders of endocrinology

Developmental Pathways

  • Indifferent Stage: In embryos, both Male (Wolffian duct developments) and Female (Mullerian duct developments) structures exist and can evolve based on hormonal influence.

  • SRY Gene:

    • The SRY gene on the Y chromosome is crucial for testis determination and functions as a master switch for male sex determination.

    • Mice with a transgene for SRY develop as males, highlighting SRY's importance, as it is responsible for influencing the gonadal development trajectory.

    • “The Elixir of youth”

    • Charles-Édouard Brown-Sequard

    • 1856 - discovers that removing the adrenal glands is lethal.postulates the existence of hormones another founder of endocrinology

    • 1889(aged 72)- reports elf medication with testis extracts from dogs and guinea pigs

    • Serge Vornoff- 1920s-30s performs testicular grafts from sheep to goats and then from monkeys to humans (Gland therapy)

Clinical Implications

  • Understanding hormone roles in sex development aids in recognizing conditions like Turner Syndrome (missing X chromosome) and Klinefelter Syndrome (additional X chromosomes affecting male development).

  • AMH levels can also serve diagnostic purposes in fertility and conditions like polycystic ovary syndrome (PCOS).

Historical Context of Endocrinology

  • The contributions of various key figures in endocrinology, such as Arnold Berthold discovering the relationship between testes and physiology, and Alfred Jost's experiments revealing the default female path of development underscore the understanding of hormones and sexual differentiation.

Summary

  • Physiological differences between the sexes are largely a result of hormonal actions that sculpt sexual development in utero, throughout childhood, and into adulthood. The interplay between genes, hormones, and environmental factors shapes individual sexual characteristics, with significant implications for health and reproductive medicine.