INTRODUCTION
The term growth hormone secretagogues (GHS) encompasses compounds that
were developed to increase the growth release of growth hormone (GH).
GHSs include growth hormone receptor secretagogue agonists (GHS-R),
whose natural ligand is ghrelin, and growth hormone-releasing hormone
(GHRH) agonists, to which GHRH binds as a native ligand [1]. Several
GHS was developed to treat or diagnose GH deficiency, namely, growth
retardation, gastrointestinal dysfunction, and changes in body
composition, in parallel to extensive research to identify GHRH, GHS-R,
and ghrelin [1].
Ghrelin is a polypeptide containing 28 amino acids that are mainly
synthesized in the stomach. Its activity stimulates GH secretion and
appetite, resulting in net body weight gain [1]. From a historical
angle, growth hormone-releasing peptides (GHRPs) were found before the
discovery of ghrelin and the ghrelin receptor. Subsequently, GHSs, that
is, ghrelin peptide mimetics, were developed. It was only later that the
GHS type 1 receptor (GHS-R1a) was discovered. Finally, ghrelin was
successfully isolated as a natural GHS-R1a ligand from stomach
substrates in 1999. This context triggered the development of ghrelin
receptor agonists, GHRPs, and GHSs; some of which have reached tests in
clinical trials [2-5].
A wide range of ghrelin receptor agonist indications has been evaluated
including growth retardation, gastrointestinal dysfunction, and altered
body composition; some of which have received approval from the Food and
Drug Administration (FDA) [6-9]. The present study focused on the
history of research and the pharmacology of ghrelin receptor agonists
[10-13]. Publicly released clinical trials on GHSs will be discussed
in this regard [14-18].
Also, in the context of selective androgen receptor modulators (SARM),
the presence of a Toll-IL-1 receptor domain (TIR) predicts a role for
SARMs in innate immunity, but SARM is very different from other TIR
proteins mammalian cytosolic MyD88, Mal, TRIF and TRAM, as it is not
necessary to signal downstream of Toll-Like (TLR) receptors [45].
Mammalian SARM was first described in 2006 as an inhibitor of TLR
signaling. Another important role for SARM is in mediating cell death
[45].
Also, a recent advance reveals that SARM is enzymes that degrade NAD +
and this activity is necessary for SARM to perform axonal destruction of
neurons [45]. Since SARM is the only protein in the TIR domain that
exhibits this activity, this suggests that at some point in the early
evolution the functions of the other TIR proteins diverged [45].
In this context, SARMs are an emerging class of therapies aimed at
cachexia, sarcopenia, and hypogonadism or treatment of stress urinary
incontinence, osteoporosis, breast cancer, and Duchenne muscular
dystrophy [46]. Since their initial scientific reports in 1998
[46], SARMs with a variety of chemical supports and pharmacological
profiles have been discovered to facilitate the selective activation of
androgen receptor (RA) tissues. RA is a member of the steroid receptor
family of ligand-activated transcription factors, which are crucial to
the organogenesis, physiology, and pathology of many tissues and are
activated by comprehensive ligands such as natural hormones, peptides,
synthetic molecules or hormones from growth [46].
The ability of SARMs to promote muscle and bone growth and strength,
inhibit the growth of breast cancer and shrink the prostate in animals
and humans is a problem based on many parameters, such as differences in
the conformation of RA, expression of the enzyme metabolizer of RA and
steroids between tissue recruitment, co-activator, and co-repressor
[47,48].
The present work aimed to present the State-of-the-Art of scientific
evidence in humans on the use of growth hormone secretagogues, SARM, and
antagonists.