Introduction
The hypothalamus, pituitary gland, and gonadal glands are referred to collectively as the hypothalamic-pituitary-gonadal axis (HPG axis), also known as the hypothalamic-pituitary-ovarian or testicular axis. The HPG axis is essential for developing and controlling several bodily systems, including the immunological and reproductive systems. Variable local and systemic effects on the body are brought on by changes in the hormones generated by each gland resulting from fluctuations in the hypothalamic-pituitary-gonadal axis.
Gonadotropin-releasing hormone-expressing neurons in the brain secrete a gonadotropin-releasing hormone (GnRH). Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are produced by the anterior pituitary gland, whereas the gonads produce estrogen and testosterone.
In females, follicle-stimulating and luteinizing hormones stimulate the ovaries to produce estrogen and control the menstrual cycles. Estrogen inhibits the hypothalamic gland's ability to produce the gonadotropin-releasing hormone, creating a negative feedback loop. A peripherally generated hormone called activin that favorably promotes gonadotropin-releasing hormone-producing cells is inhibited by inhibin. Follistatin suppresses activin and provides the rest of the body more control over the axis because it is produced in all bodily tissue. In males, luteinizing hormone induces the production of testosterone by interstitial cells in the testes, whereas follicle-stimulating hormone is involved in spermatogenesis.
What Are the Function of the Hypothalamic-Pituitary-Gonadal Axis?
1. Reproduction
The HPG axis plays a crucial role in managing reproduction by regulating the uterine and ovarian cycles. In females, the ovarian and uterine follicles are primed for ovulation and implantation due to the positive feedback loop between estrogen and luteinizing hormone. When the egg is discharged, the empty follicle sac starts to generate progesterone, which inhibits the hypothalamus and anterior pituitary and breaks the estrogen-luteinizing hormone-positive feedback loop.
Gonadotropin-releasing hormones, luteinizing hormones, and follicle-stimulating hormones are produced similarly in males, but their effects differ. Follicle-stimulating hormone induces sustentacular cells to secrete androgen-binding protein, which facilitates testosterone binding. The interstitial cells attach to luteinizing hormones, which causes them to release testosterone. Normal spermatogenesis requires testosterone, which also inhibits the hypothalamus.
2. Life Cycle
The HPG axis's activation and deactivation also contribute to the control of life cycles. In addition to having a lifetime supply of primary oocytes, females also have higher levels of follicular stimulating hormone and luteinizing hormones at birth. These levels fall throughout childhood. Estrogen or testosterone discharges from the testicles or ovaries during puberty stimulate the HPG axis. Estrogen and testosterone stimulation results in physiological and psychological changes. For the rest of their lives, the HPG axis remains inactive in men, whereas it becomes deregulated in women, resulting in menopause. The absence of oocytes, which usually produce estrogen to establish the positive feedback loop, is the primary cause of this dysregulation. Over time, the HPG axis' activity declines, and women lose fertility.
3. Sexual Dimorphism and Behavior
Due to their impact on the structure and operation of the brain, sex steroids also have an impact on behavior. Hormones play a role in the formation of sexual dimorphism by controlling the synapse and migration of neurons. Behavior variations result from these bodily disparities. Gonadotropins, sex steroids, and activin have all been demonstrated to have such effects, although gonadotropin-releasing hormone has not been proven to directly affect regulating brain structure and function. The development and differentiation of the brain are thought to be significantly influenced by follicular stimulating hormones. There is a link between prosocial conduct and testosterone levels. By fostering neurite growth and migration, it contributes to synaptogenesis. The neurotransmitters produced by peripheral neurons are controlled by activin, which also encourages neuronal plasticity throughout the lifespan. The environment can also influence hormones' relationship with behavior.
How Does Hypothalamic-Pituitary-Ovarian Axis Dysfunction Lead to Polycystic Ovarian Syndrome?
Hypogonadism is a symptom of hypothalamic-pituitary failure (HPF). Infertility, primary or secondary amenorrhea, and delayed or impaired pubertal development are common symptoms of hypothalamic-pituitary failure in females. The most frequent cause of hypothalamic-pituitary failure is idiopathic hypogonadotropic hypogonadism, which results from a congenital lack of gonadotropin-releasing hormone.
The most prevalent endocrine condition in women of reproductive age is a polycystic ovarian syndrome, which affects six to ten percent of them. It is the main reason for oligo or anovulation. Several processes characterize the etiology of polycystic ovarian syndrome, including hyperinsulinemia (increased level of insulin in the blood), ovarian insulin resistance, theca cell dysfunction, and hyperandrogenism (it is a condition characterized by an overabundance of male hormones). Loss of gonadotropin-releasing hormone pulsatility with increased luteinizing hormone release by the pituitary gland is another cause. There are abnormalities in the metabolism of androgens and estrogen as well as in the regulation of androgen production in women with the polycystic ovarian syndrome (PCOS).
Ovulation regulation is also influenced by extremes in weight and body fat distribution. Endocrine and paracrine processes that are involved in the regulation of the reproductive cycle are disrupted by obesity, especially central obesity. Reduced levels of sex hormone binding globulin (SHBG), increased production of leptin by adipocytes, and excessive aromatization of androgen precursors DHEA (dehydroepiandrosterone) and testosterone to estrone in adipose tissue are the main causes of loss of normal gonadotropin-releasing hormone pulsatility.
How to Diagnose Hypothalamic-Pituitary-Ovarian Axis Dysfunction?
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A patient's medical history can help distinguish between the different aetiologies, allowing for customized care and evaluation.
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Follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol are included in the basic examination (E2).
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In some cases, further testing is advised to rule out panhypopituitarism-associated central hypothyroidism (low TSH), hypocortisolism (low ACTH), and low growth hormone.
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To rule out morphologic pituitary irregularities or the existence of a tumor, a head MRI is recommended.
How to Treat Hypothalamic-Pituitary-Ovarian Axis Dysfunction?
The patient's needs to serve as the foundation for management principles, the main of the treatment is to cure the underlying etiology.
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Ovulation induction using exogenous gonadotropins will be beneficial for women trying to get pregnant. During ovarian stimulation, these patients need close observation.
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Commonly utilized gonadotropins include human chorionic gonadotropin (hCG), pure human menopausal gonadotropin (hMG), and recombinant follicle-stimulating hormone.
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To minimize morbidity linked to a hypoestrogenic state, sex steroid hormones must be replaced with estrogen and progesterone outside procreative management.
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Surgical excision is the line of treatment if there is the existence of a tumor.
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Pre-conceptual counseling and lifestyle modification, particularly weight loss and exercise, should be stressed before medical management.
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If pregnancy is not desired, PCOS patients frequently need a combination of oral contraceptives to inhibit their ovaries.
Conclusion
A highly controlled mechanism that manages female reproduction is the hypothalamic-pituitary-ovarian (HPO) axis. Ovulation problems brought on by HPO axis malfunction. The HPG axis is susceptible to environmental influences. Oligomenorrhea and secondary amenorrhea are common in women with eating disorders. Women's ovarian and uterine cycles end when the HPG axis becomes inactive due to anorexia nervosa or bulimia, which causes starvation. Secondary amenorrhea and oligomenorrhea have been linked to stress, physical activity, and weight reduction. Fetal alcohol spectrum disorder can emerge from prenatal alcohol exposure because it alters the hormones that control fetal development. Depending on the underlying etiology, the treatment modalities vary from patient to patient. To know more about this condition, consult the doctor online.
