Hypothalamic–pituitary–gonadal axis
The hypothalamic–pituitary–gonadal axis (HPG axis, also known as the hypothalamic–pituitary–ovarian/testicular axis) refers to the hypothalamus, pituitary gland, and gonadal glands as if these individual endocrine glands were a single entity. Because these glands often act in concert, physiologists and endocrinologists find it convenient and descriptive to speak of them as a single system.
The HPG axis plays a critical part in the development and regulation of a number of the body's systems, such as the reproductive and immune systems. Fluctuations in this axis cause changes in the hormones produced by each gland and have various local and systemic effects on the body.
The axis controls development, reproduction, and aging in animals. Gonadotropin-releasing hormone (GnRH) is secreted from the hypothalamus by GnRH-expressing neurons. The anterior portion of the pituitary gland produces luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and the gonads produce estrogen and testosterone.
In
The HPA, HPG, and HPT axes are three pathways in which the hypothalamus and pituitary direct neuroendocrine function.
Location and regulation
The
These two hormones play an important role in communicating to the gonads. In females FSH and LH act primarily to activate the
In addition, leptin and insulin have stimulatory effects and ghrelin has inhibitory effects on gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus.[5] Kisspeptin also influences GnRH secretion.[6]
Function
Reproduction
One of the most important functions of the HPG axis is to regulate reproduction by controlling the uterine and ovarian cycles.[7] In females, the positive feedback loop between estrogen and luteinizing hormone help to prepare the follicle in the ovary and the uterus for ovulation and implantation. When the egg is released, the empty follicle sac begins to produce progesterone to inhibit the hypothalamus and the anterior pituitary thus stopping the estrogen-LH positive feedback loop. If conception occurs, the placenta will take over the secretion of progesterone; therefore the mother cannot ovulate again. If conception does not occur, decreasing excretion of progesterone will allow the hypothalamus to restart secretion of GnRH. These hormone levels also control the uterine (menstrual) cycle causing the proliferation phase in preparation for ovulation, the secretory phase after ovulation, and menstruation when conception does not occur. The activation of the HPG axis in both males and females during puberty also causes individuals to acquire secondary sex characteristics.[citation needed]
In males, the production of GnRH, LH, and FSH are similar, but the effects of these hormones are different.
Life cycle
The activation and deactivation of the HPG axis also helps to regulate life cycles.
Although males remain fertile until death, the activity of the HPG axis decreases. As males age, the
Sexual dimorphism and behavior
Testosterone levels have been shown to relate to prosocial behavior.[11] This helps create synaptogenesis by promoting neurite development and migration. Activin promotes neural plasticity throughout the lifespan and regulates the neurotransmitters of peripheral neurons. Environment can also affect hormones and behavior interaction.[12]
Clinical relevance
Disorders
Disorders of the hypothalamic–pituitary–gonadal axis are classified by the World Health Organization (WHO) as:[13]
- WHO group I of ovulation disorders: Hypothalamic–pituitary failure
- WHO group II of ovulation disorders: Hypothalamic–pituitary dysfunction. WHO group II is the most common cause of ovulation disorders, and the most common causative member is polycystic ovary syndrome (PCOS).[14]
Gene mutations
Genetic mutations and chromosomal abnormalities are two sources of HPG axis alteration.[15] Single mutations usually lead to changes in binding ability of the hormone and receptor leading to inactivation or over activation. These mutations can occur in the genes coding for GnRH, LH, and FSH or their receptors. Depending on which hormone and receptor are unable to bind different effects occur but all alter the HPG axis.[citation needed]
For example, the male mutation of the GnRH coding gene could result in hypogonadotrophic hypogonadism. A mutation that cause a gain of function for LH receptor can result in a condition known as testotoxicosis, which cause puberty to occur between ages 2–3 years. Loss of function of LH receptors can cause male pseudohermaphroditism. In females mutations would have analogous effects. Hormone replacement can be used to initiate puberty and continue if the gene mutation occurs in the gene coding for the hormone. Chromosomal mutations tend to affect the androgen production rather than the HPG axis.[citation needed]
Suppression
The HPG axis can be suppressed by
The HPG axis can also be suppressed by
- GnRH agonist.
- Ovulation suppression as part of controlled ovarian hyperstimulation in in vitro fertilization, in order to prevent the spontaneous ovulation of ovarian follicles before they can be harvested.
Stimulation
Environment factors
Environment can have large impact on the HPG axis. For example, women with eating disorders tend to have oligomenorrhea and secondary amenorrhea. Starvation from anorexia nervosa or bulimia causes the HPG axis to deactivate causing women's ovarian and uterine cycles to stop. Stress, physical exercise, and weight loss have been correlated with oligomenorrhea and secondary amenorrhea.
Comparative anatomy
The HPG axis is highly conserved in the animal kingdom.[19] While reproductive patterns may vary, the physical components and control mechanisms remain the same. The same hormones are used with some minor evolutionary modifications. Much of the research is done on animal models, because they mimic so well the control mechanism of humans. It is important to remember humans are the only species to hide their fertile period, but this effect is a difference in the effect of the hormones rather than a difference in the HPG axis.
See also
- Hypothalamic–pituitary–adrenal axis
- Hypothalamic–pituitary–thyroid axis
- Hypothalamic–neurohypophyseal system
- Neuroendocrinology
- Reproductive endocrinology
References
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