Gonadorelin (GnRH) description
Peptide hormone Gonadotropin-releasing hormone (GnRH; or also known as Luteinizing hormone-heleasing hormone (LHRH)) is an agonist of the Gonadotropin-releasing hormone receptor (GnRHR; LHRHR). The international non-proprietary name for Gonadotropin-releasing hormone pharmaceutical form is Gonadorelin; and this medication is a form of the endogenous GnRH and is identical to it in chemical structure. Gonadorelin was first synthesized in 1977, and for his clarification Roger Gullemin and Andrew V. Schall received the Nobel Prize.
GnRH is produced by neuroendocrine cells within the hypothalamus. It is considered to be a neuronal hormone because it is produced by certain nerve cells. The key area for the production of GnRH is The hypothalamic preoptic area (POA), which contains most of the GnRH secreting neurons. Similar to GH (growth hormone) secretion, GnRH is also secreted pulsatilely. GnRH induces the release of gonadotropins Luteinizing hormone (LH) and Follicle-stimulating hormone (FSH) from the anterior pituitary, and its release is the first step in the system of functioning of the hypothalamo-pituitary-gonadial axis, resulting in a significant increase in testosterone blood levels in men.
GnRH mechanism of action
After secretion from the GnRH secreting neurons in The hypothalamic preoptic area, GnRH is transported by the blood via the hypothalamic-pituitary-gonadial axis to the pituitary gland, which contains gonadotropic cells, with GnRH responsive receptors – a seven-transmembrane G-protein-coupled receptor named Gonadotropin releasing hormone receptor (GnRHR).
The binding of GnRH to GnRHR subsequently activates in the pituitary gland the synthesis and secretion of gonadotropins – luteinizing hormone (LH) and follicle-stimulating hormone (FSH). These processes are controlled by the size and frequency of GnRH pulses, as well as by feedback from androgens and estrogens. Low-frequency GnRH pulses lead to FSH secretion, while high GnRH pulses stimulate LH release. GnRH is degraded by proteolysis within a few minutes.
GnRH results of action
There are differences in GnRH secretion between females and males. In males, GnRH is secreted in pulses at a constant frequency; however, in females, the frequency of the pulses varies during the menstrual cycle, and there is a large surge of GnRH just before ovulation. GnRH secretion is pulsatile in all vertebrates, and is necessary for correct reproductive function. Thus, a single hormone, GnRH1, controls a complex process of follicular growth, ovulation, and corpus luteum maintenance in the female, and spermatogenesis in the male.
GnRH also affects various sexual behaviors. Elevated GnRH levels lead to increased libido and sexual activity in women. In men, an increase in GnRH induces a sharp increase in testosterone levels, accompanied by all of its typical strong anabolic and androgenic effects.
Hypogonadism is a condition in which the male testes or the female ovaries produce little or no sex hormones. Hypogonadotropic hypogonadism (HH) is a form of hypogonadism that is due to a problem with the pituitary gland or hypothalamus. HH is caused by a lack of hormones that normally stimulate the ovaries or testes. These hormones include gonadotropin-releasing hormone (GnRH), follicle stimulating hormone (FSH) and luteinizing hormone (LH). There are several possible causes of HH such as damage to the pituitary gland or hypothalamus from surgery, injury, tumor, infection, or radiation; genetic defects; high doses or long-term use of opioid or anabolic steroids; high prolactin level (a hormone released by the pituitary); severe stress; long-term (chronic) medical diseases, including chronic inflammation or infections; or drug use..
Gonadorelin medical use
Gonadorelin can be used as a diagnostic agent to assess pituitary gland function. But its important use is also in the treatment of primary hypothalamic amenorrhea, hypogonadotropic hypogonadism, delayed puberty, cryptorchidism, infertility and impotence, thanks to its strong ability to significantly stimulate the production of sex hormones. But after a transient increase, another continuous or long administration of gonadorelin results in downregulation of LH and FSH levels followed by a suppression of ovarian and testicular steroid biosynthesis.
Other GnRH analogues, unlike Gonadorelin, are contrary often used to suppress the production of sex hormones: For example, GnRH analogue called Leuprorelin gradualy causes downregulation of GnRH receptor activity and this ultimately results in decreased LH and FSH secretion, leading to hypogonadism and thus a dramatic reduction in estradiol and testosterone levels regardless of sex, and due from this can be used to treat breast cancer, endometriosis and prostate cancer.
Scientifically investigated possible benefits of Gonadorelin
- Treatment for hypothalamic amenorrhea, hypogonadotropic hypogonadism, delayed puberty, cryptorchidism, infertility and impotence
- Pulsatile GnRH treatment can fix Hypothalamic–pituitary–gonadal axis problems and restarts Testosterone natural production
- Support muscle growth & maintenance through stimulation of testosterone production
- Positive effects for spinal cord injury recovery
- Neuroprotective effects
Gonadorelin possible side-effects
- Overdose or misuse of Gonadorelin leads to a decrease in LH and FSH levels and hypogonadism
- Hot flashes (a sudden wave of mild or intense body heat), sweating
- Injection site irritation (pain, swelling, or itching)
- Headache, nausea or dizziness
- Skin rashes
What Gonadorelin is used for?
Gonadorelin (similar as GnRH) causes the pituitary gland to release luteinizing hormone (LH) and follicle-stimulating hormone (FSH). They are important for proper development in children and fertility in adults. Therefore, gonadorelin is used in medicine as a diagnostic agent to assess pituitary gland function, or also as treatment of primary hypothalamic amenorrhea, hypogonadotropic hypogonadism, delayed puberty, cryptorchidism, infertility and impotence.
Can Gonadorelin restore testosterone production?
YES: Gonadorelin has the ability to properly restore testosterone production when used properly.
What stimulates GnRH?
GnRH is a hormone produced in the hypothalamus region of the brain. GnRH moves through the bloodstream and Hypothalamic–pituitary–gonadal axis to the pituitary gland. There, it binds to ist natural receptors Gonadotropin releasing hormone receptor (GnRHR). Those receptors signal the pituitary gland to create Luteinizing hormone (LH) and follicle-stimulating hormone (FSH).
What promotes the release of GnRH in the body?
Kisspeptin signals directly to the hypothalamic GnRH neurons via the kisspeptin receptor to release GnRH into the portal circulation, which in turn stimulates the anterior pituitary gonadotrophs to produce LH and FSH.
What inhibits GnRH release?
The GnRH neurons are regulated by many different afferent neurons, using several different transmitters (including norepinephrine, GABA, glutamate). For instance, dopamine appears to stimulate LH release (through GnRH) in estrogen-progesterone-primed females; dopamine may inhibit LH release in ovariectomized females. Kisspeptin appears to be an important regulator of GnRH release. GnRH release can also be regulated by estrogen. It has been reported that there are kisspeptin-producing neurons that also express estrogen receptor alpha.
Does testosterone inhibit GnRH?
YES: A negative feedback system occurs in the male with rising levels of testosterone acting on the hypothalamus and anterior pituitary to inhibit the release of GnRH, FSH, and LH.
What are Gonadotropic cells?
Gonadotropic cells are endocrine cells in the anterior pituitary that produce the gonadotropins, such as the follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Release of FSH and LH by gonadotropes is regulated by gonadotropin-releasing hormone (GnRH) from the hypothalamus.
What are the two Gonadotropic hormones?
Luteinizing and Follicle Stimulating Hormones. Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are called gonadotropins because stimulate the gonads – in males, the testes, and in females, the ovaries.
What is the HPG axis?
HPG axis – the hypothalamic–pituitary–gonadal axis refers to the hypothalamus, pituitary gland, and gonadal glands as if these individual endocrine glands were a single entity. 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.
How do GnRH analogues work?
GnRH analogues are agonists of the GnRH receptor and work by increasing or decreasing the release of gonadotropins by pituitary gland and the production of sex hormones by the gonads.
What gland does Gonadorelin and GnRH affect??
Gonadotropin releasing hormone (GnRH) is secreted from the hypothalamus and stimulates gonadotropic cells in the anterior pituitary gland to release luteinizing hormone and follicle-stimulating hormone, which in turn regulate the gametogenic and steroidogenic functions of the gonads in male and female.
Does GnRH cause weight gain??
Suppressing sex hormone levels with gonadotropin-releasing hormone (GnRH) agonist therapy may cause fat gain.
How does GnRH reduce estrogen?
Gonadotropin releasing hormone agonists (GnRH) are a type of medication that suppresses ovulation by stopping the production of estrogen and progesterone. In order for this axis to function properly and result in ovulation, GnRH has to be released in a pulsatile fashion.
What is the function of Gonadotropic hormone?
Gonadotropin-releasing hormone causes the pituitary gland in the brain to make and secrete the hormones luteinizing hormone (LH) and follicle-stimulating hormone (FSH). In men, these hormones cause the testicles to make testosterone. In women, they cause the ovaries to make estrogen and progesterone.
Does testosterone stimulate GnRH?
No, Testosterone inhibits gonadotropin secretion: Testosterone and/or its metabolites slows LH pulse frequency in man and inhibit LH and FSH secretion, presumably by an effect on the hypothalamic GnRH pulse generator, but it also may have a direct action on the pituitary.
Does Gonadorelin help to build muscle?
YES: It promotes muscle growth; Ipamorelin helps promote the efficient production and use of the body’s natural growth hormones, the main result are: encouraging regeneration and rejuvenation within the cells, increase in lean muscle mass, stronger bones and other above already mentioned benefits.
Usual adult dose for medical purposes in the treatment of Gonadotropin deficiency and Hypogonadotropic hypogonadism conditions is 100 mcg injected once subcutaneously or intravenously as a single dose. And the usual adult dose in the treatment of Amenorrhea is 5 mcg every 90 minutes (range of 1 to 20 mcg), delivered intravenously by a pump over 1 minute, every ninety minutes for 21 days.
Overdose or misuse of Gonadorelin leads to a decrease in LH and FSH levels and subsequent hypogonadism – a decreased functional activity of the gonads, which leads to a decrease in estrogen and testosterone production.
Gonadorelin should only be administered by a healthcare provider, and when used, the response to this drug should be monitored with LH levels, basal LH, or serum concentration of sex steroid levels during therapy as necessary.
Gonadorelin is a analogue of endogenous peptide hormone GnRH (Gonadotropin-releasing hormone). Gonadorelin (GnRH) binds to its native receptor Gonadotropin releasing hormone receptor (GnRHR), that is located in pituitary gland; what activates in the pituitary gland the synthesis and secretion of gonadotropins – luteinizing hormone (LH) and follicle-stimulating hormone (FSH). GnRH controls a complex process of follicular growth, ovulation, and corpus luteum maintenance in the female, and spermatogenesis in the male.
Gonadorelin can be used as a diagnostic agent to assess pituitary gland function, or also as treatment of primary hypothalamic amenorrhea, hypogonadotropic hypogonadism, delayed puberty, cryptorchidism, infertility and impotence, thanks to its strong ability to significantly stimulate the production of sex hormones. In such applications, however, the correct dose of Gonadorelin is very important, because misuse of Gonadorelin leads to a decrease in LH and FSH levels and subsequent hypogonadism.