Gonadorelin

Absorption

Rapidly absorbed when injected

Toxicity

LD50>3000 mg/kg (rat, oral)

The Uses of Gonadorelin

Gonadorein is a Gonadotropin-releasing hormone. Gonadorelin agonist treatment for men with locoregional prostate cancer may be associated with an increased risk of incident diabetes and ardiovascular disease.

The Uses of Gonadorelin

Gonad-stimulating principle.

Indications

For evaluating the functional capacity and response of the gonadotropes of the anterior pituitary also for evaluating residual gonadotropic function of the pituitary following removal of a pituitary tumor by surgery and/or irradiation.

Background

Gonadorelin is another name for gonadotropin-releasing hormone (GnRH). It is a synthetic decapeptide prepared using solid phase peptide synthesis. GnRH is responsible for the release of follicle stimulating hormone and leutinizing hormone from the anterior pituitary.

Definition

ChEBI: A ten-membered synthetic oligopeptide comprising pyroglutamyl, histidyl, tryptophyl, seryl, tyrosyl, glycyl, leucyl, arginyl, prolyl and glycinamide residues joined in sequence.

brand name

Lutrepulse (Ferring Pharmaceuticals).

Biological Activity

luteinizing hormone releasing hormone human acetate salt (lhrh) is a selective acitivator of mmp-2 and mmp-9 [1, 2].luteinizing hormone-releasing hormone (lhrh), also known as gonadotropin-releasing hormone (gnrh) is a trophic peptide hormone which secreted by gnrh neurons and plays an important role in the release of follicle-stimulating hormone (fsh) and luteinizing hormone (lh) from the anterior pituitary [3].mmp-2 (matrix metalloproteinase-2) and mmp-9 (matrix metalloproteinase-9) belong to the mmp family that play an important role in the breakdown of extracellular matrix (ecm) in normal physiological processes, for example, embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis [2].when tested with ishikawa and ecc-1 cell lines, lhrh resulted in the increase of mmp-9 expression which induced cell invasion and it was also showed that gpr101 mediated the lhrh activity and cooperated to function in the metastatic potential of endometrial cancer cells [1]. in human decidual endometrial stromal cells, lhrh with its receptor induced the activation of mmp-2 and mmp-9 [2].

Pharmacokinetics

Gonadorelin is responsible for the release of follicle stimulating hormone and leutinizing hormone from the anterior pitutitary. In the pituitary GnRH stimulates synthesis and release of FSH and LH, a process that is controlled by the frequency and amplitude of GnRH pulses, as well as the feedback of androgens and estrogens. The pulsatility of GnRH secretion has been seen in all vertebrates, and it is necessary to ensure a correct reproductive function. Thus a single hormone, GnRH, controls a complex process of follicular growth, ovulation, and corpus luteum maintenance in the female, and spermatogenesis in the male. Its short half life requires infusion pumps for its clinical use

Side Effects

If you experience a rare allergic reaction (difficulty breathing; closing of the throat; swelling of the lips, tongue, or face; or hives) to gonadorelin, seek emergency medical attention.
Other less serious side effects may also occur. Notify your doctor if you experience: headache; flushing; nausea or abdominal discomfort; dizziness or lightheadedness; pain, swelling, or itching at the injection site; or skin rash.

Veterinary Drugs and Treatments

Gonadorelin is indicated (approved) for the treatment of ovarian follicular cysts in dairy cattle. Additionally, gonadorelin has been used in cattle to reduce the time interval from calving to first ovulation and to increase the number of ovulations within the first 3 months after calving. This may be particularly important in increasing fertility in cows with retained placenta.
In dogs, gonadorelin has been used experimentally to help diagnose reproductive disorders or to identify intact animals versus castrated ones by maximally stimulating FSH and LH production. It has also been used experimentally in dogs to induce estrus through pulsatile dosing. While apparently effective, specialized administration equipment is required for this method.
Gonadorelin has been used in cats as an alternate therapy to FSH or hCG to induce estrus in cats with prolonged anestrus.
In Europe, a synthetic analogue buserelin has been used in horses to stimulate cyclic estrus. Its efficacy rates poorly when compared to an artificial light program, however.
In human medicine, gonadorelin has been used for the diagnosis of hypothalamic-pituitary dysfunction, cryptorchidism, and depression secondary to prolonged severe stress.

Metabolism

Rapidly hydrolyzed to inactive peptide components

References

[1]. cho-clark, m., et al., gnrh-(1-5) activates matrix metallopeptidase-9 to release epidermal growth factor and promote cellular invasion. mol cell endocrinol, 2015.
[2]. wu, h.m., et al., gonadotropin-releasing hormone type ii (gnrh-ii) agonist regulates the motility of human decidual endometrial stromal cells: possible effect on embryo implantation and pregnancy. biol reprod, 2015. 92(4): p. 98.
[3]. garnick, m.b. and m. campion, abarelix depot, a gnrh antagonist, v lhrh superagonists in prostate cancer: differential effects on follicle-stimulating hormone. abarelix depot study group. mol urol, 2000. 4(3): p. 275-7.