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9 GENERAL INTRODUCTION AND THESIS OUTLINE 1 Figure 1 . Effect of gender-affirming hormonal treatment in transgender women. Re-used from Tangpricha et al 3 , with permission from Elsevier. The hypothalamic–pituitary–gonadal axis and puberty in birth-assigned males The hypothalamic–pituitary–gonadal axis describes the system in which 3 endocrine glands (i.e. the hypothalamus, the pituitary gland, and the gonads) act in concert through secretion of hormones (Figure 2). The hypothalamus is located in the brain and secretes gonadotropin-releasing hormone (GnRH) which stimulates the pituitary gland to produce luteinizing hormone (LH) and follicle stimulating hormone (FSH). These hormones travel through the blood stream to, in their turn, stimulate the gonads to secrete sex steroids. In birth-assigned males, LH stimulates Leydig cells to produce testosterone. FSH affects - independently and in concert with testosterone - the proliferation, maturation and function of the supporting Sertoli cells that play a vital role in the maintenance of differentiating germ cells. Sertoli cells also secrete Inhibin B that, together with testosterone, acts as a negative feedbackmechanismon the hypothalamus and pituitarygland.The hypothalamic– pituitary–gonadal axis is activated by high GnRH pulsing and initiates the development of secondary sex characteristics, which marks the onset of puberty.

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