The Structure of my Least favorite Hormone: Relaxin

Relaxin is a 7 peptide hormone that is part of the insulin/IGF family. Similar to insulin, the active form of relaxin consists of two chains, linked by disulfide bridges. Studies show that no particular amino acid on the NH terminal region of the A chain is functionally important, but it is the presence of a helix that is required for biological activity (Erika et al.,1987).

RXFP1, RXFP2, RXFP3 and RXFP4 are the four receptors associated with Relaxin in humans (because I am finding it very hard to find information on this hormone with respect to other mammals). These are transmembrane G Protein coupled receptors. These glycosylated heptahelical domains are somewhat similar to FSH and LH receptors (shpakova, 2009).

Figure 1: Structural representation of Relaxin

Obtained from http://upload.wikimedia.org/wikipedia/commons/c/ce/Relaxin.png

To compare the similarity of Relaxin between species of Equus caballus (horse), Sus Scrofa (wild boar) and Felis catus (domestic cat), a sequence alignment was performed in ClustalW2, results are shown in the figure below.

Equus           -------------------------------IKACGRELARLRIEICGSLSWKKTVLRLE 29
Sus             MPRLFS-YLLGVWLLLSQLPREIPGQSTNDFIKACGRELVRLWVEICGSVSWGRTALSLE 59
Felis           MLRLFLSHLLGVWLLLSLRARKIP--AQEEVLKACGREFVRLQIRICGSLSWGKSSQQHR 58
                                               :******:.** :.****:** ::    .


Equus           EPGLEVGQPVEIVSSSISKDAEALNTKLGLNSNLPKEQKATLSERQPSWRELLQQPALKD 89
Sus             EPQLETGPPAETMPSSITKDAEILKMMLEFVPNLPQELKATLSERQPSLREL-QQSASKD 118
Felis           EPRQAPAALPEIVSSSITSGAEALNGMLEYIPDLPQELKATLSEREPSFREL--QPSLKD 116
                **    .   * :.***:..** *:  *   .:**:* *******:** ***  *.: **


Equus           SNLNLEEFEETIQKTQSEVEDDSLSELKNLGLDKHSRKKRMI--QLSHKCCYWGCT---- 143
Sus             SNLNFEEFKKIILNRQNEAEDKSLLELKNLGLDKHSRKKRLFRMTLSEKCCQVGCIRKDI 178
Felis           SNLNLEEVEKSILGRQNEAEDQSLSQLGRSRLDAHSRIKRSDYIRYSDRCCNVGCTRKEL 176
                ****:**.:: *   *.*.**.** :* .  ** *** **      *.:**  **    


Equus           ----
Sus             ARLC 182
Felis           ADLC 180

Figure 2: Alignment of relaxin in Equus caballus, Sus Scrofa (wild boar) and Felis Catus obtained in ClustalW2

- * indicates identical residues
- :  indicates there are conserveral substitutions
- .  indicates substitutions are semi-conserved

The percent similarity between each species was compared, showing that the sequence is fairly conserved between species, between 56 and 66% similarity.

Table 1. Sequence similary of the hormone Relaxin between Equus caballus, Sus Scrofa (wild boar) and Felis Catus obtained in ClustalW2

SeqA Name    Len(aa)  SeqB Name    Len(aa)  Score
=================================================
1    Equus   143      2    Sus     182      66   
1    Equus   143      3    Felis   180      58   
2    Sus     182      3    Felis   180      56   
=================================================

References

Erika,E., Bullesbach, Christian,S. (1987) "Relaxin structure, quasi allosteric effect of the nhz-terminal a-chain helix" The American Society for Biochemistry and Molecular biology, 262(26)

Shpakov, Shpakova. (2009) "Low-molecular regulators of polypeptide hormone receptors containing LGR-repeats" Biomedical Chemistry 3(4); 351-360

Hormone of choice: Relaxin

Relaxin is a peptide hormone that is very similar to insulin in structure. This hormone plays an important role during pregnancy.
Female mammals give birth through the pelvis, a strong skeletal support structure of the lower limbs. At the bottom of the pelvis, two bones are joined together at the pubic symphysis. This is a cartilaginous joint that is relatively immovable. During birth, relaxin acts on this cartilaginous joint to allow the widening of the birth canal.

Figure 1. The Pelvic Girdle, with pubic symphsis labelled

http://ajs.sagepub.com/content/29/4/521/F10.large.jpg

Relaxin is produced in granulocytes in the corpus lutueum. It has also been observed in several other places including the placenta, uterus and endometrium. Relaxin has also been found in the testes of some male animals. In males, the role of this hormone is not known. In females, the overall effect is a more flexible, wider birth canal.
Research suggests that relaxin works by cutting collagen and inducing its breakdown in the pubic symphysis. A synthetic form has been developed for the treatment of scleroderma (a connective tissue disease that causes the skin to become tight and thick).

References

1. Anderson LL, Bast JD, Melampy RM. Relaxin in ovarian tissue during different reproductive stages in the rat. J Endocrinol 59:371–372, 1973

2. Sherwood OD, Crnekovic VE, Gordon WL, Rutherford JE. Radio-immunoassay of relaxin throughout pregnancy and during parturition in the rat. Endocrinology 107:691–698, 1980.

3. Perl E, Catchpole HR, (1950). "Changes induced in the connective tissue of the pubic symphysis of the guinea pig with estrogen and relaxin", Arch Pathol (chic), 50(2): 233-239