Me: I found from this study that it may be possible to slow down or delay the closure of the growth plates at least for growth hormone deficiency adolescents with using LHRH. As stated by the study, “These results indicate that delaying puberty with LHRH-A in GHD children during treatment with GH increases final height“. Of course keep in mind that the LHRH was used in combination with GH. The test was done with a control, a group only subjected to GH, and the last group who was treated with LHRH and GH.
What I found fascinating is how the GnRH releases the right type of hormones in the anterior pituitary…“At the pituitary, GnRH stimulates the synthesis and secretion of the gonadotropins, follicle-stimulating hormone (FSH), and luteinizing hormone (LH). 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 release, whereas high-frequency GnRH pulses stimulate LH release.”
The results are…”We observed a significant decrease in the rate of BA maturation in the group treated with GH+LHRH-A (1.5 ± 0.2 yr) compared with the group treated with GH alone (4.2 ± 0.5 yr) during the 3 years of LHRH-A therapy (P < 0.05)…These results indicate that delaying puberty with LHRH-A in GHD children during treatment with GH increases final height“
Interpretation: it would seem that children treated with just GH treatment might have only increase grow velocity but did not slow the bone maturation process down. With the LHRHa, we did slow it down. This tells us a critical clue on what can be done for future research and potential ideas.
From the Wikipedia article on GnRH aka LHRH HERE we learn first what is the Luteinizing hormone releasing hormone and how it functions.
Gonadotropin-releasing hormone (GnRH), also known as Luteinizing-hormone-releasing hormone (LHRH) and luliberin, is a trophic peptide hormone responsible for the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary. GnRH is synthesized and released from neurons within the hypothalamus. The peptide belongs to gonadotropin-releasing hormone family.
GnRH is considered a neurohormone, a hormone produced in a specific neural cell and released at its neural terminal. A key area for production of GNRH is the preoptic area of the hypothalamus, which contains most of the GnRH-secreting neurons. GnRH neurons originate in the nose and migrate into the brain, where they are scattered throughout the medial septum and hypothalamus and connected by very long >1-millimeter-long dendrites. These bundle together so they receive shared synaptic input, a process that allows them to synchronize their GnRH release.
GnRH is secreted in the hypophysial portal bloodstream at the median eminence. The portal blood carries the GnRH to the pituitary gland, which contains the gonadotrope cells, where GnRH activates its own receptor, gonadotropin-releasing hormone receptor (GnRHR), a seven-transmembrane G-protein-coupled receptor that stimulates the beta isoform of Phosphoinositide phospholipase C, which goes on to mobilize calcium and protein kinase C. This results in the activation of proteins involved in the synthesis and secretion of the gonadotropins LH and FSH. GnRH is degraded by proteolysis within a few minutes.
Control of FSH and LH
At the pituitary, GnRH stimulates the synthesis and secretion of the gonadotropins, follicle-stimulating hormone (FSH), and luteinizing hormone (LH). 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 release, whereas high-frequency GnRH pulses stimulate LH release.
There are differences in GnRH secretion between females and males. In males, GnRH is secreted in pulses at a constant frequency, but, 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.
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.
Next the PubMed study link HERE
Near Final Height in Pubertal Growth Hormone (GH)-Deficient Patients Treated with GH Alone or in Combination with Luteinizing Hormone-Releasing Hormone Analog: Results of a Prospective, Randomized Trial
- M. Veronica Mericq, Martha Eggers, Alejandra Avila, Gordon B. Cutler Jr. 2 and Fernando Cassorla
- Institute of Maternal and Child Research (M.V.M., M.E., A.A., F.C.), University of Chile, Santiago, Chile; and DEB, NICHD (G.B.C.), National Institutes of Health, Bethesda, Maryland 20892
- Address correspondence and requests for reprints to: M. Verónica Mericq, IDIMI, University of Chile, Casilla 226-3, Santiago, Chile.
To study the effects of delaying puberty in GH-deficient (GHD) children, we studied 21 GHD (9 boys, 14 girls), treatment-naive, pubertal patients in a prospective, randomized trial. Their chronological age was 14.3 ± 1.6 yr, and their bone age was 11.3 ± 1.1 yr (mean ± SD) at the beginning of the study. Four patients who developed hypogonadotropic hypogonadism were subsequently excluded from the study. Patients were randomly assigned to receive GH + LH-releasing hormone analog (LHRH-A) (n = 7), or GH alone (n = 10). GH and LHRH-A treatment started simultaneously in each patient. GH (Nutropin) was administered at a dose of 0.1U/kg·day sc, until patients reached a bone age (BA) of 14 yr in girls and 16 yr in boys, and LHRH-A (Lupron depot) was administered at a dose of 300 μg/kg·every 28 days in during 3 yr. We defined GH deficiency as patients with a growth velocity less than 4 cm/yr, BA delay more than 1 yr in relationship to chronological age, GH response to two stimulation tests less than 7μ g/L, associated with low serum insulin-like growth factor I and insulin-like growth factor binding protein 3 levels. Statistical analysis was performed by ANOVA or Kruskall Wallis when variances were not homogeneous. We observed a significant decrease in the rate of BA maturation in the group treated with GH+LHRH-A (1.5 ± 0.2 yr) compared with the group treated with GH alone (4.2 ± 0.5 yr) during the 3 years of LHRH-A therapy (P < 0.05). This delay in BA maturation produced a significant gain in final height in the group treated with GH+LHRH-A, which reached −1.3 ± 0.5 SDscore compared with −2.7 ± 0.3 SD score (P < 0.05) in the group treated with GH alone. These results indicate that delaying puberty with LHRH-A in GHD children during treatment with GH increases final height.
- Received August 31, 1999.
- Revision received October 12, 1999.
- Accepted October 25, 1999.