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ENDOCRINE PHYSIOLOGY & SEX DETERMINATION

 

TABLE OF CONTENTS


Updated: Mar. 11, 2008


LECTURE INFORMATION

KEY CONCEPTS IN THIS LECTURE

1.The endocrine system consists of ductless glands which secrete hormones into the blood to act at a distant target organ. The "classic" endocrine glands are the anterior pituitary, pancreas, parathyroid, thyroid, adrenal gland, and gonads, but other organs, such as the stomach and the small intestine, also secrete hormones. The anterior pituitary gland is especially important for two reasons: 1) trophic hormones (e.g., ACTH) regulate function of other endocrine glands; and 2) the anterior pituitary is in part regulated by neural centers in the hypothalamus (=the hypothalamic-hypophyseal axis) via secretion of releasing factors (e.g., CRF).

2. There are two general classes of hormone: 1) peptide and 2) steroid. Peptide hormones readily dissolve in water while steroids do not. This difference affects how the hormones are transported in the blood as well as their action at the target cell. Peptide hormones usually act at a specific receptor on the plasma membrane. The signal is then communicated to the cytoplasm by one of the signal transduction pathways (e.g., receptor-hormone, G protein, adenylyl cyclase, cAMP, kinase). Steroids readily pass through both the plasma and nuclear membranes. They bind with a specific Hormone Response Element in the nucleus to activate DNA transcription. Hormone titer in the blood is regulated directly (blood glucose effects on insulin release) or via the hypothalamic-hypophyseal axis (inhibition of FSH by Testosterone feedback).

3. In mammals, sex is determined by the presence or absence of the Y chromosome. The Y chromosome contains a gene that produces H-Y antigen, a protein which causes differentiation of the fetal testis. Mullerian Inhibiting Factor is secreted by the fetal testis causing atrophy of the female reproductive tract. Testosterone is also secreted which stimulates the differentiation of the internal male sex organs, enlargement of the brain's sexual dimorphic nucleus, secondary sexual characteristics, and sexual behavior. If one of these events is omitted, the default state of "femaleness" occurs at that step. In other vertebrates, sex determination can be influenced by changes in the physical environment (e.g., temperature), age (e.g., younger fish are male; older fish are female), social context (e.g., absence of a male causes a female to change to a male), etc.

LECTURE OBJECTIVES

1. Compare and Contrast the general functional characteristics of peptide and steroid hormones.
2. Discuss the genetic and physiological basis for sex determination in mammals and in other vertebrates

LECTURE OUTLINE

I. AN INTRODUCTION TO THE ENDOCRINE SYSTEM **

  A. Endocrines -- ductless glands that secrete hormones 
       into the blood
     1. General characteristics
          a. often has a more general influence than nerve 
              stimulation
          b. slower onsets with longer-term effects
          c. often multiple targets are affected by single hormone

II. THE BASICS OF ENDOCRINE FUNCTION

  A. Classic endocrine glands
     1. Anterior Pituitary -- often called the "master gland" 
         because it regulates other endocrine glands (e.g., 
         gonads via tropic hormones)
           a. Prolactin is non-tropic hormone of the anterior pituitary
     2. Pancreas -- metabolism of glucose, etc.
     3. Parathroid -- Ca++ regulation
     4. Thyroid -- metabolism, but also involved in some behaviors
     5. Adrenal gland -- active during stress
     6. Testes and Ovaries -- involved in reproduction and 
         reproductive behavior

  B. General characteristics of hormones
     1. Two general classes:  1) peptides (& amines) and 2) steroids 
     2. Characteristics of peptides and steroids
          a. hydrophilic or lipophilic?
          b. site of synthesis, method of release
          c. site of hormone action
     3. Hormone action in greater detail
          a. What do all hormones have in common? (a receptor, 
              signal amplification, etc.)
          b. Peptides act at the plasma membrane
               1) Involves various membrane bound proteins and 
                   a second messenger (Animation)
          c. Steroids and thyroxine act on a receptor in the nucleus to 
              activate a hormone response (HRE) element on the
              DNA. mRNA released followed by protein synthesis 
              (Animation)
     4. Fate of circulating hormone
     5. Regulation of hormone titer in the blood
          a. Negative and Positive Feedback mechanisms
               1) Examples: Testosterone feedback & Estrogen feedback

III. SEX DETERMINATION

  A. Most organisms are diploid
     1. A karyotype reveals this diploid condition
     2. X and Y chromosomes determine sex (Female is XX
         and Male is XY)
          a. The Y is critical for "maleness"
               1) Evidence from non-disjunction
               2) Default (absence of the Y) is the female condition **

  B. What does the Y provide? 
     1. SRY gene is only on the Y chromosome
          a.  Immature reproductive system is bisexual
     2. SRY produces H-Y antigen which differentiates the 
         fetal testis
     3. Muellerian Inhibiting Factor (MIF) causes atrophy of female
         Muellerian duct
     4. Testosterone (T) stimulates:
          a. formation of internal male sex organs
          b. enlargment of the sexual dimorphic nucleus in the
              hypothalamus
          c. male behavior and secondary sexual characteristics
     5. Dihydrotestosterone (DHT) stimulates development of 
         male external genitalia
     6. Summary of Sex Determination Events **
     7.  Spotted Hyena: A unique case of sexual differentiation
          a. Female hyenas are dominant to males and are 
              very aggressive
          b. Females have external genetalia resembling that 
              of the male
          c. Fetal androgens derived from ovarian 
              4-androstenedione may be responsible for 
              masculinization. 

  C. Other influences on sex determination
     1. Other forms of genetic sex determination
          a. Birds=female is ZW and male is ZZ
     2. Temperature dependent sex determination
          a. Incubation temperature is important in some 
              ectotherms
          b. High temperatures stimulate one sex; low the other.
     3. Age of the animal may determine its sex
          a. Young black porgies are male but many change to 
              female during the third breeding season
               1) the gonad contains both ovarian and testicular 
                   tissue
          b. This process is hormonally controlled
          c. Hormone manipulations can alter the timing of sex
              reversal
     4. Behavioral sex determination
          a. Sex can change in many fish (female --> male)
          b. Sociobehavioral factors influence sex change
          c. Example: bluehead wrasse
          d. Sex may be related to GnRH level: Male fish have
              high GnRH **

STUDY QUESTIONS

  1. Review the relationship anatomical relationship between the hypothalamus and the anterior pituitary. What is characteristic of the blood-brain barrier in this brain region? Explain the significance of this. How is the circulatory system arranged here? Why? See Figure 3.19 in Carlson.

  2. The release of neurohormones from the posterior pituitary and hormones from the anterior pituitary is under different control mechanisms. Explain the nature of the differences. See Figure 3.19 in Carlson.

  3. Lipophilic hormones, such as steroids, behave differently from hydrophilic hormones. Contrast the two with respect to how they are synthesized, released, etc. Explain your answer.

  4. List the important endocrine glands in mammals? Name a hormone secreted by this endocrine gland. What is the general function(s) for each endocrine gland? Many other tissue serve an endocrine function. Can you name any of these?

  5. Define and give the physiological significance for the following terms:
    • Tropic hormone
    • Hormone
    • Neurohormone
    • Hormone response element (HRE)
    • Medial nucleus of the amygdala
    • Sexual dimorphic nucleus
    • Sex-determining region of Y (SRY)
    • Muellerian Inhibiting Factor
    • Wolffian and Muellerian ducts

  6. Steroid and peptides are different in many ways, but all hormones have certain properties in common. What are those properties? What is the physiological significance of each property?

  7. Compare and contrast steroid and peptide hormone action.

  8. Try this one. Propose an experiment (with controls) to investigate that the female condition is the default state for mammalian sex determination. What outcome would you predict if you ran the experiment. Defend your answer. You can choose any aspect of the sex determination sequence to investigate.

  9. In some vertebrates, the sex of an individual is influenced by environmental factors. List these. What is the experimental evidence that these factors are important in sex determination?

  10. Sex change of a female fish to a male fish, such as the bluehead wrasse, occurs in the absence of a male. Normally, the resident male inhibits this transition among females. What possible cues might be involved in this inhibition? Set up a controlled experiment to establish which cue is used. Given your general understanding of how the brain works, propose possible neural and endocrine elements regulating sex determination in the wrasse.

  11. What general regulatory mechanisms control hormone titer in the blood? Give examples.


ADDITIONAL INFORMATION ON THE INTERNET

Anterior and Posterior Pituitary function from the Hebrew University.

Hormone Action of peptide and steroid hormones with some animations. From Colorado State.

Sex Determination in Fish. A web page on the factors influencing sex determination in fish. Stress in fish is also discussed.


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