LECTURE 9
BRAIN AND PITUITARY GLAND
PLEASE PRINT OUT ALL FIGURES AND BRING THEM TO LECTURE

I. Introduction

a. Vertebrate reproduction is initiated and controlled by complex interactions between gonads and other organs that are not parts of the gonad or reproductive tract. Two main organs responsible for regulating gonadal functions are:

  • Brain (hypothalamus)




  • Pituitary (hypophysis)





    b. Brains and pituitary, besides regulating gonads, also regulate other aspects of reproductive physiology, such as lactation and reproductive behavior.





    c. Regulation of reproduction is achieved primarily by chemical messengers secreted into the blood = HORMONES. The secretion of these important chemical messengers is often regulated by factors acting upon the nervous system: e.g., chemical signals (smell, pheromone), visual cues, photoperiod, temperature, and tactile stimulation.





    d. Brain is the master regulatory organ or reproduction and a major interface between the environment and reproductive system.


    II. Hypothalamus and pituitary gland in mammals

    a. Developmental aspect

  • During embryonic development, the tube-like diencephalon gives rise to three regions:

    -roof -->epithalamus and epiphysis (pineal gland)




    -lateral wall-->thalamus (a relay station for sensory input)




    -floor-->hypothalamus (integration of autonomic functions and regulation of pituitary gland)

    *ventral outgrowth forms infundibulum

    **median eminence




    **stalk or stem




  • During development, the roof of the mouth (oral ectoderm) invaginates to form a small pouch called "Rathke's pouch". Rathke's pouch migrates upward and becomes associated with the infundibulum of the hypothalamus. This is the future anterior pituitary, or the adenohypophysis.




  • A part of the infundibulum close to adenohypophysis becomes the posterior pituitary, or the neurohypophysis.

  • Pituitary gland and its association with hypothalamus in adults

    See FIGURE 1

    b. Hypothalamus

  • Supraoptic/paraventricular nuclei-sends axons to and release hormones from neurohypophysis. Note that these hormones are made in the hypothalamus and neurohypophysis is only the site of release.

    -oxytocin-smooth muscle contraction, milk let-down




    -arginine vasopressin (antidiuretic hormone)-osmoregulatory hormone




    See FIGURE 2

  • hypothalamic-hypophysiotrophic nuclei-sends axons to and release hormones (hypophysiotropins) into the primary portal plexus of median eminence -->hypothalamic-pituitary portal system-->anterior pituitary. These include hormones that stimulate the anterior pituitary.

    -there are many hypophysiotropins released from the median eminence. But only one critical for the direct stimulation of gonadal function.




    -this hypophysiotrophin is called gonadotropin-releasing hormone (GnRH).
    *ten amino acids

    *both C and N terminals are protected by pyroglutamylation and amidation.




    *in mammals, this hormone is release in distinct pulses.




    *Guillemin and Schally won Nobel prize in Physiology and Medicine in 1977 for their pioneering work on the discovery of this peptide hormone.



    See FIGURE 3

    c. Pituitary

  • Neurohypophysis-the site of release of two hormones mentioned before.

    -arginine vasopressin-acts on kidney to retain water and decrease urine output.




    -oxytocin-acts primarily on smooth muscles to (1) eject milk from mammary gland, and (2) stimulate uterine contraction during labor.




  • Adenyhypophysis-the site of synthesis and release of many hormones. Many hormones are called "trophic hormones", because they are capable of exerting "trophic" (stimulatory) effects on other organs. Only two are critical for the direct regulation of gonadal function. They are collectively called "gonadotropins". Both are regulated by pulsatile GnRH stimulation. Prolonged GnRH stimulation leads to desensitization and loss of reproductive function.

    -luteinizing hormone (LH)-a large glycoprotein hormone consisting of two subunits, an alpha and a beta. Beta confers specificty.

    *in males, stimulates Leydig cells to produce testosterone (also needed for spermatogenesis).




    *in females, (1) stimulates theca cells to produce testosterone, (2) stimulates ovulation, and (3) stimulates the formation of corpus luteum.




    -follicle-stimulating hormone (FSH)-structurally related to LH. Also has alpha and beta. Alpha subunit identical to LH. Beta different.

    *in males, stimulates (1) Sertoli cell function and (2) spermatogenesis.




    *In females, stimulates (1) maturation of follicles and (2) production of estrogen (by stimulating aromatase).





    d. Integration (diagram of the Hypothalamic-Pituitary Gonadal axis)




    e. Hormonal regulation of menstrual cycle


    See FIGURE 4

    f. Importance of negative feedback of HPG axis by gonadal steroids

  • Athletes taking anabolic steroids (androgens)

    -both LH and FSH inhibited




    -no spermatogenesis because no FSH




    -little endogenous testosterone synthesis




  • Women on birth control pills (a combination of low doses of estrogen and progesterone)

    -both LH and FSH inhibited




    -no follicular growth because of no FSH




    -no ovulation because of no LH





    III. Comparative aspects of HPG axis

    a. There are three ways that hypophysiotropins can reach the pituitary to regulate the secretion of pituitary hormones.

  • Diffusional--used by the most primitive fishes (cyclostomes).
    Can be done by diffusion of hormones into the pituitary. There is no specialized portal circulation to take hypothalamic hormone to the pituitary.



    See FIGURE 5



  • Neurovascular--used by chonstrichthyes, osteichthyes (except teleost), and tetrapods. Have a special portal vasculature to carry hypophysiotropins directly from the median eminence to the pituitary.



    See FIGURE 6



  • Neuroglandular--Used exclusively by teleosts. Represents a highly-evolved state. Axons of neurons in hypothalamus penetrate into the pituitary and directly innervate the pituitary, releasing the hypophysiotropins directly onto the specific pituitary cell type.



    See FIGURE 7