Chemistry: natural resins or derivatives; peptides or proteins; – Peptides of 3 to 100 amino acid residues – Lutenizing hormone releasing factor ; related peptides
Patent
1994-01-17
1996-05-14
Chan, Christina Y.
Chemistry: natural resins or derivatives; peptides or proteins;
Peptides of 3 to 100 amino acid residues
Lutenizing hormone releasing factor ; related peptides
530327, 530328, A61K 3824, C07K 723
Patent
active
055168876
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
This invention relates to novel peptide antagonists of luteinizing hormone.
BACKGROUND OF THE INVENTION
In the mammal, the anterior pituitary gland is located at the base of the brain, but is separate from it. A special set of closed circulation blood vessels connect the anterior pituitary to the brain at the region of the hypothalamus. It is the activity of the hypothalamus which largely regulates the production of luteinizing hormone, (LH), and follicle stimulating hormone, (FSH), by the anterior pituitary.
Within the hypothalamus, neurosecretory cells manufacture and release gonadotropic releasing hormones such as luteinizing hormone releasing hormone, (LHRH), also know as gonadotropic releasing hormone, (GnRH). LHRH enters a closed system of blood vessels directly connecting the hypothalamus with the anterior pituitary. As LHRH contacts neurosecretory cells located within the anterior pituitary these cells are stimulated to release luteinizing hormone into the systemic blood stream. In a similar manner, the hypothalamus causes the anterior pituitary to release FSH.
A developing mammalian egg, an oocyte grows to maturation within an ovarian follicle. Cyclically, the hypothalamus secretes follicle stimulating hormone releasing factor into the closed capillary system attaching the hypothalamus to the anterior pituitary. Once FSHRH contacts the anterior pituitary, it stimulates neurosecretory cells to produce FSH. FSH causes the mammalian follicle to grow both in size and number of cells. The follicle cells in turn secrete estrogen which stimulates the growth of the uterine wall in preparation for implantation of an embryo should fertilization occur. A feedback phenomenon occurs as estrogen level production stimulated by FSH rise causing both a direct reduction in the output of FSH by the anterior pituitary as well as an indirect effect by means of reducing hypothalamic stimulus of the anterior pituitary.
As the follicle reaches full maturity, the hypothalamus responds to the rising estrogen levels by secreting LHRH or luteinizing hormone releasing hormone into the closed capillary system connecting the hypothalamus with the anterior pituitary. As LHRH reaches the anterior pituitary, it stimulates release of luteinizing hormone. Luteinizing hormone stimulates the completion of maturation of the follicle and ovum. LH is also known as interstitial cell-stimulating hormone since it acts upon the interstitial cells of the testes in stimulating production of testosterone. After the mature follicle has released an ovum into the oviduct, the corpus luteum, which is derived from the remnant granulosa and theca cell of the ruptured follicle cells, becomes the equivalent of an endocrine gland secreting progesterone under the influence of LH.
If a fertilized egg is implanted, chorionic gonadotropin or CG is secreted by the placental tissues. CG prevents the corpus luteum from degenerating and allows it to continue its production of progesterone. Progesterone maintains the growth of cells of the endometrium as well as maintaining an adequate blood supply to nourish an implanted embryo.
Normally, as outlined above, the function of LH and FSH are biologically positive. FSH stimulates the mammalian follicle to produce estrogens while LH stimulates the corpus luteum to produce progesterone and the interstitial cells of the testes and ovaries to produce testosterone and estrogen respectively. FSH and LH have a synergism. That is to say, LH, when administered by itself has little or no effect, but combined with a small dose of FSH induces follicular maturation. Likewise, a small amount of LH greatly augments the response of the response of tissue to a small amount of FSH. For this reason, LHRH antagonists also affect the activity of FSH.
The above discussed hormones may be classified as gonadotropic as they stimulate growth and function of reproductive tissue. However, there are certain situations in which the gonadotropic effects of these hormones may deleteriously affect the health of an individual. Ce
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Chan Christina Y.
Deghenghi Romano
Prickril Benet
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