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Date sent: Tue, 28 Oct 1997 10:59:20 -0600
From: wiltbank@calshp.cals.wisc.edu
Subject: Re: PGF and CL
I am responding to earlier postings about cloprostenol and subsequent
luteal function.

We have done some research to evaluate the half-life of cloprostenol.  In
sheep it is surprisingly short (~2 min).  This brief exposure to PGF2a will
obviously regress the mature corpus luteum.  However, administration of
PGF2a on day 4 of the cycle did not alter progesterone concentrations as
measured until day 11 of the cycle in a recent study that we did (In press
for Biol of Reprod in Feb 1998).

Thus, I do not think a direct action on the subsequent corpus luteum is
likely.  It is more likely that cloprostenol altered the function of the
follicle that later became the corpus luteum.  We have evaluated the
preovulatory follicle for receptor to PGF2a and found almost no mRNA for
this receptor in either granulosa or thecal cells of the preovulatory
follicle (before or 24 hr after the LH surge).  Induction of expression of
mRNA for PGF2a receptor (more than 1,00-fold induction began about 1 day
after ovulation (Endocrinology 137:3348; 1996).  This is a time that would
be well after all the cloprostenol is degraded.

If there is a difference in luteal function after PGF2a in some studies and
not in other studies as suggested by Dr. Fields then I would hypothesize
that this difference may be primarily due to the state of follicular
development at the time of PGF2a.  Normal regression of the corpus luteum
usually occurs after "deviation" of the dominant follicle and production of
high amounts of estradiol.  This has been demonstrated by a few different
labs that have removed or inhibited growth of the dominant follicle.
Regression of the corpus luteum is delayed if follicular growth is
inhibited.

If the corpus luteum is regressed with PGF (analog or not) the future
ovulatory follicle may be at any stage of follicular development.  If PGF2a
were administered on day 7 (or other time when a fully grown follicle were
present on the ovary) then the large dominant follicle would probably
produce a fully functional corpus luteum.  If PGF2a is administered at a
time prior to deviation then the follicle may cause an early LH surge.  The
subsequent corpus luteum would be produced from a follicle with fewer cells
(less time for growth) and  would be likely to produce a corpus luteum that
produces less progesterone.  Matt Lucy of Univ of Missouri has shown me
data that ovulation of a smaller follicle produces a corpus luteum that
produces less progesterone throughout the luteal phase (all days of cycle
examined) and we now have similar data for size of the corpus luteum on day
7 and 14 after ovulation of a larger or smaller follicle.

Thus, I would speculate that differences between studies or between animals
may be due to the size or function of the follicle that is ovulated after a
PGF2a injection.  Past studies by Harry Momont and Brad Seguin at
University of Minnesota found no difference between lutalyse or estrumate
in time to estrus or other parameters that I can remember.  They did report
a large difference in time to estrus due to day of the estrous cycle on
which PGF was administered, probably because of stage of follicular
development.  Sorry to be so long-winded.

Milo

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Milo Wiltbank
Department of Dairy Science
University of Wisconsin-Madison
Madison, WI 53706
608-263-9413
Wiltbank@Calshp.cals.wisc.edu