Metastin, compounds that promote the activity of metastin or its receptors and the like are excellent gonadal function improving agents, ovulation inducers or promoters, gonadotropic hormone secretion promoters, gonadotropic hormone secretion inhibitors, sex hormone secretion promoters, sex hormone secretion inhibitors, etc., and can be used as agents for preventing/treating sterility, hormone-sensitive cancers, endometriosis, etc. Metastin and its receptors are useful for screening for these pharmaceuticals.

Description of the Invention

Under the present circumstances, the present inventors made extensive investigations and have thus found that human metastin has a gonadotropin release-promoting effect, a gonadal function improving effect, an ovulation promoting effect, etc. The inventors have further clarified that ovulation by metastin is a phenomenon of ovulation mediated by normal differentiation of estrogen-producing granulosa cells into progesterone-producing luteal cells, and continuous administration of metastin reduces the release of gonadotropins and production of testosterone in the testis. As a result of further studies, the inventors have come to accomplish the present invention.

More specifically, the present invention relates to the following features, and so on.

(1) A gonadal function improving agent, which comprises a polypeptide comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 1, or a salt thereof.

(2) The gonadal function improving agent according to (1), which comprises a polypeptide consisting of the amino acid sequence represented by SEQ ID NO: 3, or a salt thereof.

(2a) The gonadal function improving agent according to (1), which comprises a polypeptide consisting of the amino acid sequence represented by SEQ ID NO: 9, SEQ ID NO: 11, SEQ ID NO: 13 or SEQ ID NO: 15, or a salt thereof.

(3) The gonadal function improving agent according to (1), wherein the amino acid sequence which is substantially the same as the amino acid sequence represented by SEQ ID NO: 1 is the amino acid sequence represented by SEQ ID NO: 2.

(3a) The gonadal function improving agent according to (1), which comprises a polypeptide consisting of the amino acid sequence represented by SEQ ID NO: 5, or a salt thereof.

(3b) The gonadal function improving agent according to (1), which comprises a polypeptide consisting of the amino acid sequence represented by SEQ ID NO: 7, or a salt thereof.

(4) A gonadal function improving agent, which comprises a polynucleotide encoding a polypeptide comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 1, or a salt thereof.

(4a) A gonadal function improving agent, which comprises a polynucleotide consisting of the base sequence represented by SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 12, SEQ ID NO: 14, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18 or SEQ ID NO: 19.

(5) A gonadal function improving agent, which comprises a compound or its salt that promotes the activity of a polypeptide comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 1, or a salt thereof.

(5a) The gonadal function improving agent according to (5), wherein the compound is a compound that promotes the activity of a polypeptide consisting of the amino acid sequence represented by SEQ ID NO: 3, or a salt thereof.

(6) A gonadal function improving agent, which comprises a compound or its salt that promotes the activity of a protein comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 20, its partial peptide, or a salt thereof.

(7) A gonadal function improving agent, which comprises a compound or its salt that promotes the activation of a polypeptide comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 1, or a salt thereof, into a protein comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 20, its partial peptide, or a salt thereof.

(8) The gonadal function improving agent according to (1) through (7), which is an agent for preventing/treating sterility.

(9) The gonadal function improving agent according to (1) through (7), which is an ovulation inducer or promoter.

(10) The gonadal function improving agent according to (1) through (7), which is a gonadotropic hormone secretion promoter.

(11) The gonadal function improving agent according to (1) through (7), which is a gonadotropic hormone secretion inhibitor.

(12) The gonadal function improving agent according to (1) through (7), which is a sex hormone secretion promoter.

(12a) The gonadal function improving agent according to (12), wherein the sex hormone is an androgen (testosterone, androstenedione, etc.), an estrogen (estradiol, estrone, etc.) or progesterone.

(13) The gonadal function improving agent according to (1) through (7), which is a sex hormone secretion inhibitor.

(13a) The gonadal function improving agent according to (13), wherein the sex hormone is an androgen (testosterone, androstenedione, etc.), an estrogen (estradiol, estrone, etc.) or progesterone.

(14) The gonadal function improving agent according to (1) through (7), which is an agent for preventing/treating a hormone-sensitive cancer.

(15) The gonadal function improving agent according to (1) through (7), which is an agent for preventing/treating endometriosis.

(16) A diagnostic agent for sterility, which comprises a polynucleotide encoding a polypeptide comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 1, or a salt thereof, or a polynucleotide encoding a protein comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 20, its partial peptide, or a salt thereof.

(17) A diagnostic agent for sterility, which comprises an antibody to a polypeptide comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 1, or a salt thereof, or an antibody to a protein comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 20, its partial peptide, or a salt thereof.

(18) A method of screening for a gonadal function improving agent, which comprises using a polypeptide comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 1, or a salt thereof, and/or a protein comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 20, its partial peptide, or a salt thereof.

(19) The screening method according to (18), wherein the gonadal function improving agent is a sex hormone secretion inhibitor or a sex hormone secretion promoter.

(20) The screening method according to (18), wherein the gonadal function improving agent is a gonadotropic hormone secretion inhibitor or a gonadotropic hormone secretion promoter.

(21) A kit for screening for a gonadal function improving agent, which comprises a polypeptide comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 1, or a salt thereof, and/or a protein comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 20, its partial peptide, or a salt thereof.

(22) A method of screening for a gonadal function improving agent, which comprises using a polynucleotide encoding a polypeptide comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 1, or a salt thereof, and/or a polynucleotide encoding a protein comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 20, its partial peptide, or a salt thereof.

(23) A kit for screening for a gonadal function improving agent, which comprises a polynucleotide encoding a polypeptide comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 1, or a salt thereof, and/or a polynucleotide encoding a protein comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 20, its partial peptide, or a salt thereof.

(23a) A gonadal function improving agent, which is obtainable using the screening method according to (18) or (22), or using the screening kit according to (21) or (23).

(23b) The gonadal function improving agent according to (23a), which is an agent for preventing/treating sterility.

(23c) The gonadal function improving agent according to (23a), which is an ovulation inducer or promoter.

(23d) The gonadal function improving agent according to (23a), which is a gonadotropic hormone secretion promoter or inhibitor.

(23e) The gonadal function improving agent according to (23a), which is a sex hormone secretion promoter or inhibitor.

(24) A method of improving gonadal function, which comprises administering to a mammal an effective dose of (i) a polypeptide comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 1, or a salt thereof, (ii) a polynucleotide encoding said polypeptide or a salt thereof, (iii) a compound or its salt that promotes the activity of said polypeptide or a salt thereof, (iv) a compound or its salt that promotes the activity of a protein comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 20, its partial peptide, or a salt thereof, or (v) a compound or its salt that promotes the activation of said polypeptide or a salt thereof into said protein, its partial peptide, or a salt thereof.

(25) A method of improving gonadal function, which comprises (i) promoting the activity of a polypeptide comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 1, or a salt thereof, (ii) promoting the activity of a protein comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 20, its partial peptide, or a salt thereof, or (iii) promoting the activation of said polypeptide or a salt thereof into said protein, its partial peptide, or a salt thereof.

(26) Use of (i) a polypeptide comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 1, or a salt thereof, (ii) a polynucleotide encoding said polypeptide or a salt thereof, (iii) a compound or its salt that promotes the activity of said polypeptide or a salt thereof, (iv) a compound or its salt that promotes the activity of a protein comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 20, its partial peptide, or a salt thereof, or (v) a compound or its salt that promotes the activation of said polypeptide or a salt thereof into said protein, its partial peptide, or a salt thereof, to manufacture a gonadal function improving agent.

(27) A method of inhibiting gonadotropic hormone secretion and/or a method of inhibiting sex hormone secretion, which comprises uninterruptedly or continuously administering to a mammal an effective dose of (i) a polypeptide comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 1, or a salt thereof, (ii) a polynucleotide encoding said polypeptide or a salt thereof, (iii) a compound or its salt that promotes the activity of said polypeptide or a salt thereof, (iv) a compound or its salt that promotes the activity of a protein comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 20, its partial peptide, or a salt thereof, or (v) a compound or its salt that promotes the activation of said polypeptide or a salt thereof into said protein, its partial peptide, or a salt thereof.

(27a) A method of inhibiting gonadotropic hormone secretion, which comprises administering to a mammal an effective dose of (i) a polypeptide comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 1, or a salt thereof, (ii) a polynucleotide encoding said polypeptide or a salt thereof, (iii) a compound or its salt that promotes the activity of said polypeptide or a salt thereof, (iv) a compound or its salt that promotes the activity of a protein comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 20, its partial peptide, or a salt thereof, or (v) a compound or its salt that promotes the activation of said polypeptide or a salt thereof into said protein, its partial peptide, or a salt thereof, which dose is sufficient to inhibit gonadotropic hormone secretion, which dose is sufficient to inhibit gonadotropic hormone secretion.

(27b) A method of inhibiting sex hormone secretion, which comprises administering to a mammal an effective dose of (i) a polypeptide comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 1, or a salt thereof, (ii) a polynucleotide encoding said polypeptide or a salt thereof, (iii) a compound or its salt that promotes the activity of said polypeptide or a salt thereof, (iv) a compound or its salt that promotes the activity of a protein comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 20, its partial peptide, or a salt thereof, or (v) a compound or its salt that promotes the activation of said polypeptide or a salt thereof into said protein, its partial peptide, or a salt thereof, which dose is sufficient to inhibit sex hormone secretion, which dose is sufficient to inhibit sex hormone secretion.

(27c) A method of inhibiting gonadotropic hormone secretion, which comprises administering to a mammal an effective dose of an agonist for a protein comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 20, its partial peptide, or a salt thereof, which dose is sufficient to inhibit gonadotropic hormone secretion, which dose is sufficient to inhibit gonadotropic hormone secretion.

(27d) A method of inhibiting sex hormone secretion, which comprises administering to a mammal an effective dose of an agonist for a protein comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 20, its partial peptide, or a salt thereof, which dose is sufficient to inhibit sex hormone secretion, which dose is sufficient to inhibit sex hormone secretion.

(27e) A method of inhibiting gonadotropic hormone secretion, which comprises retaining in a mammal at the site or tissue where the pharmaceutical effects are to be exhibited, at a level more than required, (i) a polypeptide comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 1, or a salt thereof, (ii) a polynucleotide encoding said polypeptide or a salt thereof, (iii) a compound or its salt that promotes the activity of said polypeptide or a salt thereof, (iv) a compound or its salt that promotes the activity of a protein comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 20, its partial peptide, or a salt thereof, or (v) a compound or its salt that promotes the activation of said polypeptide or a salt thereof into said protein, its partial peptide, or a salt thereof.

(27f) A method of inhibiting sex hormone secretion, which comprises retaining in a mammal at the site or tissue where the pharmaceutical effects are to be exhibited, at a level more than required, (i) a polypeptide comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 1, or a salt thereof, (ii) a polynucleotide encoding said polypeptide or a salt thereof, (iii) a compound or its salt that promotes the activity of said polypeptide or a salt thereof, (iv) a compound or its salt that promotes the activity of a protein comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 20, its partial peptide, or a salt thereof, or (v) a compound or its salt that promotes the activation of said polypeptide or a salt thereof into said protein, its partial peptide, or a salt thereof.

(27g) A method of inhibiting gonadotropic hormone secretion, which comprises retaining in a mammal at the site or tissue where the pharmaceutical effects are to be exhibited, at a level more than required, an agonist for a protein comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 20, its partial peptide, or a salt thereof.

(27h) A method of inhibiting sex hormone secretion, which comprises retaining in a mammal at the site or tissue where the pharmaceutical effects are to be exhibited, at a level more than required, an agonist for a protein comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 20, its partial peptide, or a salt thereof.

(28) A method of preventing/treating a hormone-sensitive cancer or endometriosis, which comprises uninterruptedly or continuously administering to a mammal an effective dose of (i) a polypeptide comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 1, or a salt thereof, (ii) a polynucleotide encoding said polypeptide or a salt thereof, (iii) a compound or its salt that promotes the activity of said polypeptide or a salt thereof, (iv) a compound or its salt that promotes the activity of a protein comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 20, its partial peptide, or a salt thereof, or (v) a compound or its salt that promotes the activation of said polypeptide or a salt thereof into said protein, its partial peptide, or a salt thereof.

(28a) A method of preventing/treating a hormone-sensitive cancer or endometriosis, which comprises administering to a mammal an effective dose of (i) a polypeptide comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 1, or a salt thereof, (ii) a polynucleotide encoding said polypeptide or a salt thereof, (iii) a compound or its salt that promotes the activity of said polypeptide or a salt thereof, (iv) a compound or its salt that promotes the activity of a protein comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 20, its partial peptide, or a salt thereof, or (v) a compound or its salt that promotes the activation of said polypeptide or a salt thereof into said protein, its partial peptide, or a salt thereof, which dose is sufficient to give a preventive/therapeutic effect on the hormone-sensitive cancer or endometriosis.

(28b) A method of preventing/treating a hormone-sensitive cancer or endometriosis, which comprises administering to a mammal an effective dose of an agonist for a protein comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 20, its partial peptide, or a salt thereof, which dose is sufficient to give a preventive/therapeutic effect on the hormone-sensitive cancer or endometriosis.

(28c) A method of preventing/treating a hormone-sensitive cancer or endometriosis, which comprises retaining in a mammal at the site or tissue where the pharmaceutical effects are to be exhibited, at a level more than required, (i) a polypeptide comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 1, or a salt thereof, (ii) a polynucleotide encoding said polypeptide or a salt thereof, (iii) a compound or its salt that promotes the activity of said polypeptide or a salt thereof, (iv) a compound or its salt that promotes the activity of a protein comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 20, its partial peptide, or a salt thereof, or (v) a compound or its salt that promotes the activation of said polypeptide or a salt thereof into said protein, its partial peptide, or a salt thereof.

(28d) A method of preventing/treating a hormone-sensitive cancer or endometriosis, which comprises retaining in a mammal at the site or tissue where the pharmaceutical effects are to be exhibited, at a level more than required, an agonist for a protein comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 20, its partial peptide, or a salt thereof.

(29) A method of inhibiting follicular maturation and/or a method of suspending a menstrual cycle, which comprises uninterruptedly or continuously administering to a mammal an effective dose of (i) a polypeptide comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 1, or a salt thereof, (ii) a polynucleotide encoding said polypeptide or a salt thereof, (iii) a compound or its salt that promotes the activity of said polypeptide or a salt thereof, (iv) a compound or its salt that promotes the activity of a protein comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 20, its partial peptide, or a salt thereof, or (v) a compound or its salt that promotes the activation of said polypeptide or a salt thereof into said protein, its partial peptide, or a salt thereof.

(29a) A method of inhibiting follicular maturation and/or a method of suspending a menstrual cycle, which comprises administering to a mammal an effective dose of (i) a polypeptide comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 1, or a salt thereof, (ii) a polynucleotide encoding said polypeptide or a salt thereof, (iii) a compound or its salt that promotes the activity of said polypeptide or a salt thereof, (iv) a compound or its salt that promotes the activity of a protein comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 20, its partial peptide, or a salt thereof, or (v) a compound or its salt that promotes the activation of said polypeptide or a salt thereof into said protein, its partial peptide, or a salt thereof, which dose is sufficient to inhibit the follicular maturation and/or suspend the menstrual cycle.

(29b) A method of inhibiting follicular maturation and/or a method of suspending a menstrual cycle, which comprises administering to a mammal an effective dose of an agonist for a protein comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 20, its partial peptide, or a salt thereof, which dose is sufficient to inhibit the follicular maturation and/or suspend the menstrual cycle.

(29c) A method of inhibiting follicular maturation and/or a method of suspending a menstrual cycle, which comprises retaining in a mammal at the site or tissue where the pharmaceutical effects are to be exhibited, at a level more than required, (i) a polypeptide comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 1, or a salt thereof, (ii) a polynucleotide encoding said polypeptide or a salt thereof, (iii) a compound or its salt that promotes the activity of said polypeptide or a salt thereof, (iv) a compound or its salt that promotes the activity of a protein comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 20, its partial peptide, or a salt thereof, or (v) a compound or its salt that promotes the activation of said polypeptide or a salt thereof into said protein, its partial peptide, or a salt thereof.

(29d) A method of inhibiting follicular maturation and/or a method of suspending a menstrual cycle, which comprises retaining in a mammal at the site or tissue where the pharmaceutical effects are to be exhibited, at a level more than required, an agonist for a protein comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 20, its partial peptide, or a salt thereof.

(30) A method of promoting gonadotropic hormone secretion and/or a method of promoting sex hormone secretion, which comprises applying bolus administration to a mammal in an effective dose of (i) a polypeptide comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 1, or a salt thereof, (ii) a polynucleotide encoding said polypeptide or a salt thereof, (iii) a compound or its salt that promotes the activity of said polypeptide or a salt thereof, (iv) a compound or its salt that promotes the activity of a protein comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 20, its partial peptide, or a salt thereof, or (v) a compound or its salt that promotes the activation of said polypeptide or a salt thereof into said protein, its partial peptide, or a salt thereof.

(30a) A method of promoting gonadotropic hormone secretion and/or a method of promoting sex hormone secretion, which comprises administering to a mammal an effective dose of (i) a polypeptide comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 1, or a salt thereof, (ii) a polynucleotide encoding said polypeptide or a salt thereof, (iii) a compound or its salt that promotes the activity of said polypeptide or a salt thereof, (iv) a compound or its salt that promotes the activity of a protein comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 20, its partial peptide, or a salt thereof, or (v) a compound or its salt that promotes the activation of said polypeptide or a salt thereof into said protein, its partial peptide, or a salt thereof, which dose is sufficient to promote the gonadotropic hormone secretion and/or promote the sex hormone secretion.

(30b) A method of promoting gonadotropic hormone secretion and/or a method of promoting sex hormone secretion, which comprises retaining in a mammal at the site or tissue where the pharmaceutical effects are to be exhibited, at a level more than required, (i) a polypeptide comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 1, or a salt thereof, (ii) a polynucleotide encoding said polypeptide or a salt thereof, (iii) a compound or its salt that promotes the activity of said polypeptide or a salt thereof, (iv) a compound or its salt that promotes the activity of a protein comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 20, its partial peptide, or a salt thereof, or (v) a compound or its salt that promotes the activation of said polypeptide or a salt thereof into said protein, its partial peptide, or a salt thereof.

(31) A method of inducing or promoting ovulation, which comprises applying bolus administration to a mammal in an effective dose of (i) a polypeptide comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 1, or a salt thereof, (ii) a polynucleotide encoding said polypeptide or a salt thereof, (iii) a compound or its salt that promotes the activity of said polypeptide or a salt thereof, (iv) a compound or its salt that promotes the activity of a protein comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 20, its partial peptide, or a salt thereof, or (v) a compound or its salt that promotes the activation of said polypeptide or a salt thereof into said protein, its partial peptide, or a salt thereof.

(31a) A method of inducing or promoting ovulation, which comprises administering to a mammal an effective dose of (i) a polypeptide comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 1, or a salt thereof, (ii) a polynucleotide encoding said polypeptide or a salt thereof, (iii) a compound or its salt that promotes the activity of said polypeptide or a salt thereof, (iv) a compound or its salt that promotes the activity of a protein comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 20, its partial peptide, or a salt thereof, or (v) a compound or its salt that promotes the activation of said polypeptide or a salt thereof into said protein, its partial peptide, or a salt thereof, which dose is sufficient to induce or promote ovulation.

(31b) A method of inducing or promoting ovulation, which comprises retaining in a mammal at the site or tissue where the pharmaceutical effects are to be exhibited, at a level more than required, (i) a polypeptide comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 1, or a salt thereof, (ii) a polynucleotide encoding said polypeptide or a salt thereof, (iii) a compound or its salt that promotes the activity of said polypeptide or a salt thereof, (iv) a compound or its salt that promotes the activity of a protein comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 20, its partial peptide, or a salt thereof, or (v) a compound or its salt that promotes the activation of said polypeptide or a salt thereof into said protein, its partial peptide, or a salt thereof.

(32) A method of inhibiting ovulation, a method of regulating ovarian function, a method of preventing/treating a hormone-sensitive cancer or a method of preventing/treating endometriosis, which comprises administering to a mammal an effective dose of (i) a compound or its salt that inhibits the activity of a polypeptide comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 1, or a salt thereof, (ii) an antibody to said polypeptide or a salt thereof, (iii) an antisense nucleotide to a polynucleotide encoding said polypeptide or a salt thereof, (iv) a compound or its salt that inhibits the activity of a protein comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 20, its partial peptide, or a salt thereof, (v) an antibody to the polypeptide or a salt thereof, or (vi) an antisense polynucleotide to a polynucleotide encoding said protein, its partial peptide, or a salt thereof.

(32a) A method of inhibiting ovulation, a method of regulating ovarian function, a method of preventing/treating a hormone-sensitive cancer or a method of preventing/treating endometriosis, which comprises administering to a mammal an effective dose of an antagonist to a protein comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 20, its partial peptide, or a salt thereof.

Claim 1 of 2 Claims

1. A method of inhibiting secretion of follicle-stimulating hormone and testosterone in a male mammal, comprising continuously administering to said male mammal an effective dose of a polypeptide comprising the amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 11, SEQ ID NO: 13, and SEQ ID NO: 15.

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