Treatment of sex hormone binding globulin (SHBG) related diseases by inhibition of natural antisense transcript to SHBG

1. A method of upregulating a function of and/or the expression of a Sex Hormone Binding Globulin (SHBG) polynucleotide having SEQ ID NO: 1 in patient cells or tissues in vivo or in vitro comprising: contacting said cells or tissues with at least one antisense oligonucleotide 12 to 30 nucleotides in length wherein said at least one oligonucleotide is specific for a natural antisense polynucleotide of the SHBG gene having SEQ ID NOS: 2 or 3 and has at least 80% sequence identity to a reverse complement of a polynucleotide comprising 12 to 30 consecutive nucleotides within nucleotides 1 to 3016 of SEQ ID NO: 2 or nucleotides 1 to 1609 of SEQ ID NO: 3; thereby upregulating a function of and/or the expression of the Sex Hormone Binding Globulin (SHBG) polynucleotide in patient cells or tissues in vivo or in vitro.

2. A method of upregulating a function of and/or the expression of a Sex Hormone Binding Globulin (SHBG) polynucleotide having SEQ ID NO: 1 in patient cells or tissues in vim or in vitro comprising: contacting said cells or tissues with at least one antisense oligonucleotide 15 to 30 nucleotides in length wherein said oligonucleotide is specific for a natural antisense polynucleotide of the SHBG gene having SEQ ID NOS: 2 or 3 and has at least 80% sequence identity to a 15 to 30 nucleotide region of an RNA polynucleotide transcribed from the SHBG gene or a polynucleotide derived therefrom; thereby upregulating a function of and/or the expression of the Sex Hormone Binding Globulin (SHBG) polynucleotide in patient cells or tissues in vivo or in vitro.

3. A method of upregulating a function of and/or the expression of a Sex Hormone Binding Globulin (SHBG) polynucleotide having SEQ ID NO: 1 in patient cells or tissues in vivo or in vitro comprising:

contacting said cells or tissues with at least one antisense oligonucleotide of 15-30 nucleotides in length that specifically targets a 15 to 30 nucleotide region of a natural antisense polynucleotide of the Sex Hormone Binding Globulin (SHBG) polynucleotide wherein said natural antisense polynucleotide comprises SEQ ID NOS: 2 or 3; thereby upregulating a function of and/or the expression of the Sex Hormone Binding Globulin (SHBG) polynucleotide in patient cells or tissues in vivo or in vitro.

4. The method of claim 3 , wherein a function of and/or the expression of the Sex Hormone Binding Globulin (SHBG) is increased in vivo or in vitro with respect to a control.

5. The method of claim 3 , wherein the at least one antisense oligonucleotide targets a natural antisense sequence of a Sex Hormone Binding Globulin (SHBG) polynucleotide selected from SEQ ID NOS: 2.

6. The method of claim 3 , wherein the at least one antisense oligonucleotide targets a natural antisense polynucleotide antisense to coding and/or non-coding nucleic acid sequences of a Sex Hormone Binding Globulin (SHBG) RNA polynucleotide.

7. The method of claim 3 , wherein the at least one antisense oligonucleotide targets a natural antisense polynucleotide having overlapping and/or non-overlapping sequences with a Sex Hormone Binding Globulin (SHBG) RNA polynucleotide.

8. The method of claim 3 , wherein the at least one antisense oligonucleotide comprises one or more modifications selected from: at least one modified sugar moiety, at least one modified internucleoside linkage, at least one modified nucleotide, and combinations thereof.

9. The method of claim 8 , wherein the one or more modifications comprise at least one modified sugar moiety selected from: a 2′-O-methoxyethyl modified sugar moiety, a 2′-methoxy modified sugar moiety, a 2′-O-alkyl modified sugar moiety, a bicyclic sugar moiety, and combinations thereof.

10. The method of claim 8 , wherein the one or more modifications comprise at least one modified internucleoside linkage selected from: a phosphorothioate, alkylphosphonate, phosphorodithioate, alkylphosphonothioate, phosphoramidate, carbamate, carbonate, phosphate triester, acetamidate, carboxymethyl ester, and combinations thereof.

11. The method of claim 8 , wherein the one or more modifications comprise at least one modified nucleotide selected from: a peptide nucleic acid (PNA), a locked nucleic acid (LNA), an arabino-nucleic acid (FANA), an analogue, a derivative, and combinations thereof.

12. The method of claim 1 , wherein the at least one oligonucleotide comprises at least one oligonucleotide sequences set forth as SEQ ID NOS: 4 to 17.

13. A method of upregulating a function of and/or the expression of a Sex Hormone Binding Globulin (SHBG) gene encoding SEQ ID NO: 1 in mammalian cells or tissues in vivo or in vitro comprising:

contacting said cells or tissues with at least one short interfering RNA (siRNA) oligonucleotide 19 to 30 nucleotides in length, said at least one siRNA oligonucleotide being specific for a natural antisense polynucleotide of a Sex Hormone Binding Globulin (SHBG) polynucleotide selected from SEQ ID NOS: 2 or 3; and, upregulating a function of and/or the expression of Sex Hormone Binding Globulin (SHBG) in mammalian cells or tissues in vivo or in vitro.

14. A method of upregulating a function of and/or the expression of Sex Hormone Binding Globulin (SHBG) having SEQ ID NO: 1 in mammalian cells or tissues in vivo or in vitro comprising: contacting said cells or tissues with at least one antisense oligonucleotide of about 20 to 30 nucleotides in length specific for a natural antisense strand of a Sex Hormone Binding Globulin (SHBG) polynucleotide wherein said natural antisense strand comprises SEQ ID NOS: 2 or 3 and wherein said at least one antisense oligonucleotide has at least 80% sequence identity to a 20 to 30 nucleotide region of at least one nucleic acid sequence set forth as SEQ ID NOS: 1 or a polynucleotide encoded by the SHBG gene; and, upregulating the function and/or expression of the Sex Hormone Binding Globulin (SHBG) in mammalian cells or tissues in vivo or in vitro.