1. AN ONLINE TUTORIAL

2. CONTENTS HOW TO USE THIS TUTORIAL OBJECTIVES INTRODUCTION AND DEFINITION COMPONENTS OF THE AXIS THE HYPOTHALAMUS THE PITUITARY THE OVARIAN UNIT INTERGRATION OF THE AXIS, CONTROL AND REGULATION OESTRADIOL NEGATIVE FEDBACK OESTRADIOL POSITIVE FEEDBACK: PROGESTERONE: INHIBINS AND OTHER PEDTIGENIC HORMONES REGULATION OF GnRH BY KISSPEPTIN NEUROTRANSMITTER REGULATION of GnRH REFERENCES

3. HELP ON HOW TO USE THIS TUTORIAL EFFECTIVELY  Click on the underlined hyperlinks for resource material.  Click on the audio icon for an audio narrative.  Use the animation and additional info links if more in-depth material is required

4. OBJECTIVES OF THIS TUTORIAL  To understand the components of hypothalamo-pituitary-ovarian axis.  How they interact for normal function.  Effects of normal function.  Control of normal function.

5. THE HPO AXIS DEFINITION INTRODUCTION INTRODUCTION The hypothalamo-pituitary-ovarian axis is essentially a complex but necessary interplay between the hypothalamus, the pituitary and the ovaries in such a way that they behave like one neuroendocrine organ. The axis is functionally involved in the development of primary and secondary sexual characteristics, the control of oogenesis and by extension reproduction.

6. COMPONENTS OF THE AXIS ANIMATION ANIMATION HYPOTHALAMUS PULSATILE GnRH THE PITUITARY LH FSH THE OVARIAN UNIT ESTRADIOL POSITIVE FB PROGESTERONE NEGATIVE FB FIG 1: THE COMPONENTS OF THE NORMAL HPO AXIS

7. THE HYPOTHALAMUS ANATOMY PHYSIOLOGY ANATOMY PHYSIOLOGY The female reproductive system is coordinated normally with influences from within the classical model which has the GnRH pulse generator located within the hypothalamus as the primary structure that drives the axis. It releases the decapeptide gonadotrophin-releasing hormone GnRH that stimulates the gonadotropes in the anterior pituitary to produce luteinising hormone (LH) and follicle stimulating hormone (FSH). The GnRH molecule

8. THE HYPOTHALAMUS ANATOMY PHYSIOLOGY ANATOMY PHYSIOLOGY GnRH is produced and released from specialized neurons located within the arcuate nucleus initially as a part of a large prohormone which is modified in the axons as they extend into the median eminence where GnRH bearing axons terminate on loops of the hypophyseal portal system within in the anterior pituitary sinusoids. The structure of GnRH is common to all mammals and has similar functions in both sexes.

9. THE PITUITARY ANATOMY PHYSIOLOGY ANATOMY PHYSIOLOGY The gonadotropins, LH and FSH, are synthesized within the gonadotrophs in the anterior pituitary gland located in the sella turcica of the sphenoid bone. They are both glycoprotein hormones comprising α and β subunits. The β subunit confers hormone specificity and function while the α subunit is common to LH, FSH, human chorionic gonadotropin (HCG) and thyroid-stimulating hormone (TSH). Functional activity of these hormones require the presence of both subunits.

10. THE OVARIAN UNIT PHYSIOLOGY PHYSIOLOGY LH and FSH elicit responses from the female gonads; the ovaries, causing morphologic changes and active secretion of the female steroid sex hormones. Oestrogen and progesterone.

11. THE OVARIAN UNIT PHYSIOLOGY PHYSIOLOGY Morphologic effects can be grouped into effects that comprise the ovarian cycle/ folliculogenesis i.e., the cyclical recruitment of follicles from the ovarian reserve. Which under the phasic concentrations of LH and FSH will lead to the production of one dominant mature follicle ready for ovulation and the formation of a corpus luteum after ovulation.

12. INTERGRATION OF THE AXIS, CONTROL AND REGULATION ANIMATION ANIMATION Control and communication between the hypothalamic-pituitary unit and the ovaries is essential for the normal physiology of the reproductive cycle and the functions required of it. It is important for the higher components of the axis (hypothalamus and pituitary) to modulate their secretions in response to the secretions and activity the ovary.

13. INTERGRATION OF THE AXIS, CONTROL AND REGULATION The pituitary secretion of LH and FSH is influenced by the following, Hypothalamic GnRH pulse frequency and amplitude, The number of GnRH receptors, Post receptor signaling, Phasic negative and positive feed- back effects from estradiol,progesterone, peptides (inhibin) kisspeptins, and neurotransmitter substances.