Growth hormone deficiency may also develop in adults due to brain injury, a pituitary tumour or damage to the pituitary gland for example, after brain surgery or radiotherapy for cancer treatment.
The main treatment is to replace the growth hormone using injections - either once a day or several times a week. In the past, growth hormone treatment was stopped at the end of growth. It is now clear that growth hormone contributes to both bone mass and muscle mass reaching the best possible level, as well as reducing fat mass during development to an adult.
The specialist is therefore likely to discuss the benefits of continuing growth hormone after growth has completed until age 25 to make sure bone and muscle mass reach the best possible level.
Additionally, growth hormone has been linked to a sensation of wellbeing, specifically energy levels. These adults may benefit from lifelong treatment with growth hormone. Taking growth hormone when adult will not result in increased height. About Contact Events News. Search Search. You and Your Hormones. Students Teachers Patients Browse. As such, the IGF protein family continues to be a viable target for new therapeutic agents.
Dwarfism can result from a mutation in the hepatic GH receptor which yields insensitivity to secreted GH. As a consequence, IGF-1 is synthesized and secreted at suboptimal levels. Should hormone excess present after epiphyseal plate fusion, the condition is referred to as acromegaly. Both disorders are extremely rare and symptoms can be intermittent, often confounded by coexisting conditions. The common therapeutic approach for these disorders is aimed at regulating circulating GH and IGF-1 levels using recombinant hormone therapy, 8 but ongoing in vitro and in vivo studies are employing newer methods of treatment.
To date, treatments have the greatest impact when started prior to puberty. When IGF-1 binds to IGF-1R, the tyrosine kinase activates the phosphoinositide 3-kinase PI3K -AKT pathway and many integral proteins involved in cellular metabolism, apoptosis, cell adhesion, and angiogenesis are regulated within this pathway.
Numerous in vitro and in vivo studies have been performed that focused on the modulation of total and free IGF-1 levels and relative impact on tumor growth, invasiveness and response to therapeutics.
IGF-1 is highly homologous with insulin and can readily bind to the insulin receptor IR. This is not surprising when considering that daily sc administration of GH is unable to mimic the endogenous pattern resulting from pituitary GH release, which allows insulin to act independently due to postprandial suppression of GH. With more prolonged GH therapy, the favorable effects on body composition may offset the direct insulin antagonistic effects, in particular if attention is paid to avoid overdosing.
Insulin resistance as a side effect to GH administration is no less surprising than the risk of hypoglycemia with insulin therapy. Studies of a more experimental nature with GH in GHDA have also provided new insight into the mechanisms underlying the metabolic effects such as the close link between the lipolytic effects and the resistance to insulin-induced glucose disposal in muscle, and the important protein-conserving effect of GH during fasting.
Moreover, studies in GHDA have generated novel data on the impact of GH on features such as cardiac function, bone metabolism, lipoprotein metabolism, thyroid hormones, and regional glucocorticoid interconversion, most of which has been beyond the scope of this review. Due to its anabolic and lipolytic properties, GH has also been administered in different catabolic states such as the frail elderly with sarcopenia and obese patients undergoing caloric restriction.
At the present stage, it is important to emphasize that metaanalyses of published data do not justify GH as either an antiaging treatment or as adjunct treatment in obesity So-called rejuvenation of GH secretion in the elderly by means of GH secretagogues has also been evaluated, including a recent long-term trial , , and it does again remain a possibility that some in this age group could benefit from more sophisticated anabolic regimens, e.
GH treatment in HIV-associated wasting has been shown in several randomized controlled trials to increase LBM and body weight and to improve physical endurance and quality of life, and GH is a Food and Drug Administration-approved indication for this condition.
It remains to be further investigated whether GH treatment also may cause a sustainable beneficial effect on HIV-associated lipodystrophy.
Elevation of blood glucose levels is a frequent side effect of GH also in these patients. The fatal outcome of trials involving patients with acute critical illness as well as the serious complications of acromegaly underscore more than anything that GH treatment outside of the approved indications should not be based on wishful thinking, but rather be confined to appropriately controlled and rigorously monitored trials.
Having said this, a worthy subject for future research would be to dissect whether the detrimental effects of GH in acute critical illness are due to metabolic aberrations or hitherto unrecognized proinflammatory actions. Medical treatment of acromegaly is another area that has undergone major improvements and also provided further insight into the metabolic effects of GH.
Treatment with slow-release formulations of somatostatin analogs is well established and provides symptom relief, disease control, and tumor shrinkage in a large proportion of patients. It does, however, also cause a mild impairment of glucose tolerance, in many cases owing to the fact that its suppressive effect on insulin secretion is not always fully balanced by the concomitant improvement of insulin sensitivity.
The GHR antagonist, pegvisomant, seems to provide a more complete suppression GH bioactivity, which also includes reversal of glucose intolerance and insulin resistance. Indeed, this compound may even induce functional GH deficiency in patients with acromegaly. Data generated so far suggest that cotreatment with somatostatin analogs and pegvisomant may offer a favorable combination of tumor control and peripheral blockade.
Moreover, pegvisomant is an interesting experimental tool for studying the metabolic actions of GH in other conditions. Future vistas of research related to the metabolic effects of GH are multiple, and not all of them have been addressed in this review. The discovery of ghrelin as an endogenous ligand for the so-called GH secretagogue receptor is one example.
This gut-derived peptide is not only a potent stimulator of GH release when administered exogenously, but it also possesses independent effects on substrate metabolism and appetite regulation, which are just beginning to be unveiled. Moreover, it remains to be assessed to what degree endogenous gut-derived ghrelin drives GH secretion.
Another white spot on the map is the role of GH as a fat-burning cytokine in the regulation of adipokines and myokines, which may have implications for the understanding of fundamental conditions such as obesity, cardiovascular disease, and aging processes. Exciting progress within the research of the regulation and function of the GH-IGF-I axis during life span continues to be made, and surprises are hopefully ahead.
But data so far confirm the statement by Bernardo A. Disclosure Summary: N. Gen Comp Endocrinol : 3 — Google Scholar. J Biol Chem : — Diabetologia 49 : — Diabetes 50 Suppl 1 : S25 — S Am J Hum Genet 14 : — Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus.
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Diabetologia 33 : 52 — Critique of dawn and meal phenomena. Diabetes 38 : — However, capacitated sperm from these mice were able to fertilize oocytes Furthermore, IGF was demonstrated to increase responsiveness of porcine Leydig cells to physiological hCG concentrations and to pharmacological steroidogenesis activators This stimulatory effect was enhanced significantly when IGF functioned in unison with FSH, echoing the response observed in female granulosa cells It has been reported that IGF promoted thymidine inclusion in DNA of Sertoli cells and to have role as a mitogenic stimulator in immature Sertoli cells 8.
Furthermore, it can regulate glucose and lactate metabolism in Sertoli cells, which are crucial metabolites for germ cell health It also stimulates plasminogen activator production in Sertoli cells 8 , 83 , 95 , which is secreted by Sertoli cells and plays an important role in germ cell development, formation, and migration These effects in testicular biology, along with that of GH are summarized in Table 1.
This process can upregulate the expression of steroidogenic genes such as those encoding aromatase and StAR, along with the LHR gene , The aromatase gene is directly regulated by CREB , and this enzyme converts androgens e. Akt is a multifunctional signaling hub that can regulate cell metabolism, proliferation, and death 36 , 95 , Interestingly, recent research in human and rodent granulosa cells has shown that intact IGF-1R signaling was also required for FSHR-mediated phosphorylation of Akt 66 , IGF and proinsulin share homology such that both of their respective receptors, IGFR and the insulin receptor IR , will bind to the alternate growth factors albeit with reduced affinity 3.
However, further studies are required, particularly in male reproductive organs, to confirm if this mechanism exists. The vast majority of GH actions are mediated through the JAK-STAT signaling events which has multiple complex roles, such as regulating cell proliferation and oocyte maturation Figure 1 , and significant downstream crosstalk with the other pathways 42 , These components go on to increase cytosolic calcium flux from organelles and activate PKC, respectively.
In granulosa cells, p38 MAPK plays a role in generating pro-apoptotic signals Thus, this interplay and individual participation of MAPK signaling in steroidogenesis remains unclear. Since steroid hormones are not stored in large quantities in steroidogenic tissues, there is constant demand for cholesterol, the main precursor of steroidogenesis Consequently, steroidogenic cells have numerous, small lipid droplets that contain cholesteryl esters that release free cholesterol upon stimulation by hormones.
HSL was found to be expressed in internal and external theca cells as well as granulosa cells of preantral follicles ATGL was detected in granulosa and Leydig cells , Conversely, it has been reported that GH may indirectly enhance ATGL expression in vivo through an unknown mechanism, but the effects of ATGL in steroidogenic cells in the ovary and testes requires further research Interestingly, it has been shown that ERK can directly phosphorylate HSL at Ser increasing the enzyme activity in adipocyte cell lines 42 , GH and IGF have the ability to alter the direction of lipid metabolism via regulation of these enzymes and this may have important implications for lipid homeostasis in steroidogenic cells and tissues, especially those derived from the reproductive system where GH is used regularly as an adjuvant for fertility treatment.
However, little research has explicitly explored this area in reproduction. The downstream signaling from FSH-FSHR interactions is clearly central to the life and death balance observed in granulosa cells and developing follicles, and seems to have parallels in male reproductive cells.
GH is regularly used as an adjuvant in fertility treatment, and studies in animal and ex vivo human models demonstrate that GH and IGF regulate steroidogenesis, cell proliferation, and follicular development. While this area of research has undoubtedly progressed, it is still not completely clear which biochemical mechanisms are involved. The concept of this review was designed by JY and KK. The initial manuscript draft was undertaken by EI and KK.
All artwork produced by VC. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors acknowledge kind sponsorship by Ferring Pharmaceuticals to support in vitro experimental work to determine the role of GH in carbohydrate and lipid metabolism in granulosa cell lines performed in the laboratory of KK and JY.
Ferring Pharmaceutical have had no input on the current review article. Involvement of growth hormone GH and insulin-like growth factor IGF system in ovarian folliculogenesis. Receptors for lactogenic hormones in the ovine corpus luteum. I: a major discrepancy in the specific binding of radiolabelled ovine prolactin and human growth hormone.
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Growth hormone enhances follicle-stimulating hormone-induced differentiation of cultured rat granulosa cells.
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