Abstract
| Grant Number: |
2S06GM045455-120011 |
| PI Name: |
LIN, YU-WAI P. |
| PI Email: |
|
| PI Title: |
|
| Project Title: |
Gonadal Peptide Effect on Female
Reproduction--Activins |
Abstract: Folliculogenesis in vertebrates involves the developmental
progression from a small primordial follicleto a large preovulatory follicle
containing a fully competent oocyte arrested at the second meiotic metaphase
by the time of ovulation. This entire process is regulated and coordinated by
endocrine hormones such as the pituitary gonadotropins, and locally modulated
by steroids and factors (inhibin/activin) acting
in an autocrine/paracrine manner. The molecular nature of these factors is
only now being elucidated. Gonadal peptides such as inhibin and
activin are currently being recognized not only as regulators of
the pituitary gonadotropins secretion, but also as multifunctional modulators
in the ovary and in the utero-placental unit. In addition to their normal
reproductive roles, inhibins and activins have been implicated in gonadal
oncogenesis and pathologies of the reproductive system. In this regard, high
levels of inhibin B are associated with granulosa cell
carcinoma, and high levels of inhibin A are correlated with
pre-eclampsia and Down syndrome during pregnancy. The understanding of the
relationship of several gonadal peptides to the signals for gonadal function
still has many unanswered questions. This proposal is designed to elucidate
the molecular mechanisms underlying the expression and the paracrine and
autocrine biological activities of inhibin/activin
A and B. Although the different inhibin/activin
isoforms (A and B) appear to have similar effects in the pituitary, there is
also precedent suggesting that they may have distinct physiological roles in
different tissues. The availability of recombinant
inhibin/activin A and B now gives the possibility
to assess the functions of the various
inhibin/activin isoforms. In order to implement
the above objectives, the following projects will be carried out:: a)
Isolation and cloning of the inhibin/activin
subunits (alpha,betaA,and betaB) from ovarian tissue, b) Antibodies against
the inhibin/activin subunits will be generated to
carry out western blot analysis, c) Expression of
inhibin/activin subunits during follicle
development and during the process of gonadotropic stimulation of oocyte
maturation, d) Paracrine (local effect at neighboring cells) and autocrine
(local effect in the same cells) biological activities (on steroidogenesis and
oocyte maturation) of inhibin/activin A and B will
be assessed using in vitro ovarian follicle cultures, to test the hypothesis
that the various forms of the gonadal peptides may have distinct physiological
roles in the ovary. The proposed research will furnish critically needed
information about the molecular dynamics and actions of the
inhibin/activin in the ovary. Understanding the
physiology of inhibins and activins and the interplay of major endocrine and
paracrine mechanisms involved in the ovary is essential to decipher the
process of gonadal differentiation in both normal and disease conditions, and
may ultimately help in the diagnosis and treatment of reproductive dysfunction
in humans.
Thesaurus Terms:
activin, female reproductive
system, graafian follicle, hormone regulation /control mechanism,
inhibin, oogenesis, protein structure function
autocrine,
gonad, gonadotropin, messenger RNA, paracrine, peptide hormone
Osteichthyes, RNase protection assay, molecular cloning, nucleic acid
sequence, polymerase chain reaction, radioimmunoassay, tissue /cell culture,
western blotting
| Institution: |
BARRY UNIVERSITY |
|
11300 NE 2ND AVE |
|
MIAMI, FL 33161 |
| Fiscal Year: |
2003 |
| Department: |
|
| Project Start: |
01-MAY-2003 |
| Project End: |
30-APR-2007 |
| ICD: |
NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES |
| IRG: |
MPRC |
  
|
