An Introduction to the Hypothalamic–Pituitary–Gonadal Axis

The hypothalamic–pituitary–gonadal axis (HPG axis) plays an important role in  the  development  and  regulation of a number of the body’s systems, such as the immune and reproductive systems. Fluctuating hormone levels cause changes in the hormones that are produced by each gland and as a result have a variety of widespread and local effects in the body. The HPG axis can be influenced by lifestyle and dietary factors such as stress, inadequate  sleep, illness, the use of certain medications including hormones, as well as poor dietary habits. This axis can also be subject to disorders such  as hypothalamic–pituitary failure or dysfunction, as occurs in ovulation disorders, one example being polycystic ovary syndrome (PCOS).

Female hormones affect reproductive organs and also influence several other body functions by interacting with major neuro-endocrine systems including thyroid hormones, stress hormones, and the autonomic nervous system. The HPA (hypothalamic-pituitary-adrenal) axis is affected by similar factors as the HPG axis and involves the hypothalamus, pituitary and adrenal glands as well as the hormones CRH (corticotropin-releasing hormone), ACTH (adrenocorticotropic hormone) and the stress hormone known as cortisol which is necessary to survive. Therefore, a lack of normal functioning of the female reproductive system impacts a wide variety of other emotional and physical health conditions. HPG axis refers to the effects of the hypothalamus, pituitary gland, and gonads as if these separate endocrine glands were a single entity acting as a whole. Since the glands often function in cooperation, endocrinologists and physiologists find it more simple and descriptive to refer to them as a single system. The HPG axis controls reproduction, development, and aging. The hypothalamus produces gonadotropin-releasing hormone (GnRH). The anterior portion of the pituitary gland produces luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and the gonads produce estrogen and testosterone. The hypothalamus is located in the brain and secretes GnRH. GnRH moves down the anterior portion of the pituitary and binds to the secretory cell receptors of the anterior pituitary.

In response to stimulation from GnRH, these cells then produce LH and FSH, which enters into the blood stream. These two hormones have a significant role in communicating to the gonads. FSH and LH act primarily to activate the ovaries to produce estrogen and inhibin and to regulate the menstrual cycle and ovarian cycle in females

Symptoms of HPG Axis Dysfunction

The most common cause of hot flashes in menopausal women is changing levels of estrogen in the body. Diminished amounts of estrogen have a direct effect on the hypothalamus, the part of the brain responsible for controlling appetite, sex hormones, sleep, and body temperature. Lowered levels of estrogen confuse the hypothalamus, causing it to inaccurately sense that the body is overheating. This provokes an internal chain of reactions that women experience as “hot flashes”. Sudden weight gain in women may also be caused by hormone imbalance. Since the hypothalamus is responsible for metabolism and body temperature, when the hypothalamus isn’t functioning normally, this can slow metabolism, also causing the thermogenic process for fat burning to slow, thus causing significant weight increase.

HPG Axis’ Role in Female Reproduction and Development

One ofthemost important functions of the HPG axis is to regulate reproduction by influencing the ovarian and uterine cycles. In females, a positive feedback loop between luteinizing hormone and estrogen assists in preparing the follicle in the ovary and the uterus for ovulation and implantation. At the time the egg is released, the ovary starts to produce progesterone to inhibit the hypothalamus and the anterior pituitary, therefore stopping the estrogen-LH positive feedback loop. If conception does occur, the fetus will assume the role of secreting progesterone; causing the mother to be unable to ovulate again. If conception does not occur, reduced progesterone excretion will allow the hypothalamus to restart secretion of GnRH. These hormone levels also influence the menstrual cycle initiating the proliferation phase to prepare for ovulation, the secretory phase after ovulation, and menstruation when conception does not occur. HPG axis activation in both males and females during puberty also causes individuals to gain secondary sex characteristics. HPG axis activation and deactivation also helps to regulate life cycles. FSH and LH levels are elevated at birth, and females have a lifetime supply of the primary cells from which an egg develops (oocytes). These levels decrease and remain lower throughout childhood. At puberty the HPG axis is activated by estrogen secreted from the ovaries or testosterone from the testes. Physiological and psychological changes are caused by the activation of estrogen and testosterone. After being activated, the HPG axis functions in men for the rest of their life but becomes deregulated in women which leads to menopause. The deregulation is caused mainly by the reduction in oocytes that normally produce estrogen to create the positive feedback loop. Over many years, HPG axis activity decreases and women cease to be fertile. Balancing the HPG axis throughout life is important since it significantly affects temperature regulation, metabolism, weight control, mood and also the aging process. Lifestyle factors and dietary choices as well as supplements and medications can all profoundly affect the functioning of this system.

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