BIOLOGY

OF

REPRODUCTION

47,

149-161

Follicle-Stimulating

(1992)

Hormone

Plays

Cysts

a Role

of South

Carolina

Induction

in Hypophysectomized KATRYNA

University

in the

School Columbia,

of Ovarian

Follicular

Rats

BOGOVICH’

of Medicine, Department South Carolina 29208

of Obstetrics

& Gynecology

ABSTRACT stimulation

Unabated immature To

rats

and

determine

whether

immature

beginning

hCG)

beginning

in the

ovaries

on

treated

the

with rats.

Serum

progesterone concentrations

In

all

in

and enhanced

but and

did not estradiol

the

first

initial

fofficles

induction ovarian

for

all

follicles

in follicular

any

of ovarian

cysts

cysts

from

other

group

in the

in this

+

rats

treated

any

day

tested.

rat and

that

combined,

Ovarian

follicular

because

required tion

for

either

or normal

mone

cysts

develop

of a disruption normal

follicular

profiles

and

atresia

polycystic

sively monal

for both animals and interactions required

ovarian

follicular

Unabated

stimulation

ovarian cysts and pregnant pect

cysts

of both

[1-8].

state

have

been

women, for the

cohort

of developing

matase

activity.

concept

that

This chronic

serum

the

characterized

yet

to be

elucidated.

by

low

doses

of hCG

is the

cysts

possess

most

observation

contrasts

stimulation

by elevated

from

FSH

University

were

rats

unabated

stimulation

those

rats

of controls. in vivo

with

increased

FSH-treated

by FSH

may

and

androincubation

HYPOXD

rats,

Both androstenedlone groups. In addition,

estradiol

FSH

treatment

progesterone

in the

animals. treatment

Serum HYPOXD

in vitro

testosterone

more

throughout treatment).

+ hCG-treated other

and

for control

(thCG

any

and

that

estradiol

HYPOXD

to cAMP

produced indicate

only

follicles

observed

increased

hCG.treated,

hCG

largest follicles ovaries from

to

or

+

the

values

from

for

(FSH

whereas

FSH

responded

hCG largest

treatment

with

and

ovaries, daily

the

control

from

of follicles

results

0FSH

analyzed,

similar

androstenedione

+

These

once

In contrast,

5 of FSH

(cAMP)

control,

(0FSH)

diestrus.

of age),

above

from FSH + hCG-treated for follicles from all in vivo

in the play

an

LH-like

presence

of

important

activity

can

that

role

is sufficient

amounts sharply serum

of South

Carolina

similar

potential role to be explored.

rats as-

used the determine

first

ity of

of aro-

to

stimulate the devel-

[1-3].

to those

immature rats is maintained

FSH

observed

on

diestrus

[11, 121 at con[15].

the

synchronized

of

SC 29208.

149

also in women and animals cystic ovaries [1-81. Nevertheless,

hypophysectomized whether FSH

unabated

cyst

but

for FSH in follicular cyst development The series of experiments described has

stimulation

ovarian follicular were age-matched

LH and

School

cysts

cysts [9, 10, 16-221 “naturally” occurring

induce

with

of ovarian

of FSH provokes

In-

terestingly, chronically maintained serum FSH activlty seems to be common not only in all models used to study ovarian

horof

the

interferes with the ability cell function and thereby

centrations

ian Accepted March 25, 1992. Received January 27, 1992. ‘Correspondence: Dr. Katr na Bogovich, Medicine, Building 28, First Floor, Columbia,

40

and

3 and

cAMP

FSH both

steroids

elevated

incubates

cystic

In both progesterone-synchronized and pregnant rats [13, 14] serum

exten-

immature remarkable

observation large

serum

groups

opment

establishment

have

models

an-

hor-

the fundamental initial development

in progesterone-synchronized rats [9, 10]. Perhaps the of these

other

interactions

Although after

(Day

of fofficles/cysts

androgens granulosa

development/ovula-

function

of the

and

hormonal

follicular

ovarian

ovary

in humans

in the

or

on

induce

species.

INTRODUCTION

imals

of age;

for hCG-treated

hCG-treated

with

on

ovine

observed

to

of development.

Of the

ng of either

incubates

activity

of development,

stage

Days

than

in follicular incubates under these conditions

follicles/cysts from

similar

8-bromo

FSH

28

progesterone-synchronized to those

2 jg

treatments

treatment

of 400

Day

consistently

Incubates to

of LH-like

stage

between

estradiol and

on

antral

were

in both similar

(control);

37 of age.

were

responded Inclusion

accumulation markedly

Day

+ hCG

treatment,

FSH-treated

in vitro.

small

gonadotropin and

groups

from

preantral

elevated

in vivo

ability

in vivo

at the

values were

of the

cysts

at values

hormone

at the by

FSH

in vivo

accumulation

follicular

cysts with

by any

accumulation

of developing than

and

the

beginning

end

were

fotlicular

androstenedione,

progesterone

cohort

rats

no

13 days

By the

follicular models

affects

either

for

atretic

treatment

enhance progesterone production increased

testosterone induce

values

vivo

only

estradiol

daily

steroids

ovarian of these

FSH

given

treated

affected

progesterone,

from

were

were

these

not

serum

dihydrotestosterone

contrast, estrone

basal

HYPOXD large

and

produces in both

respectively.

displayed

were

However,

stenedione

28, animals

testosterone

more

Follicles

accumulation.

to

Day

for animals

and

contained

in the

twice

IU hCG

hCG-treated

+ hCG

treatments.

insulin

medium

0.5

FSH-treated

FSH

Serum

group.

and

from

by rats

and

activity

is maintained

(HYPOXD)

concentrations

in vivo

rats

27

FSH

stimulation

27;

Day

of control

androstenedione HYPOXD

Day

of LH.like

Serum

unabated on

in ovaries

present

doses

low rats.

hypophysectomized

14 days

rats

by

pregnant

by

cysts. The to the rats

induction

animals intact,

previously

used

[11, 12].

study

(0.5

licles

by Day

IU twice

10 of treatment

daily)

with

intact,

immature,

(HYPOXD) a significant

The

with a

has yet here

immature rat to impact on the abil-

LH-like

activity

to

induce

used in the present study immature, progesteroneby this dose

induced in our

lab to study

of hCG cystic

and

dose-response

progesterone-synchronized

used precystic

ovarin this folstudies rats

150

BOGOVICH

[11,

12].

The

because

it

dose

of FSH

is the

preovulatory

dose

used

used

follicular

in this

work

by investigators

development

was

selected

to study

in the

HE3F2

tam the weight of 1 mm2. Then the images were divided by this standard

normal rat model

MATERIALS Animals

and

AND

METHODS

millimeters

for

each

ovarian

cross

sec-

Serum Serum

Histology

Immature

female

rats,

HYPOXD

were

addition to the Carolina (USC, were provided

rat chow provided by the University of South Columbia, SC) Animal Resource Facility, and with water containing 10% sucrose. A re-

housed

were

(Boston, MA). fed oranges

describing the in vivo aspects by the USC Animal Use Committee.

in groups

controlled

Laboratories animals

of age,

Charles viability,

search protocol was approved

River these

at 21 days

obtained from help maintain

of 5-6

room

on

per

container

a 12L:12D

cycle

To in

of this study Rats were

in a temperaturewith

lights

on

at 0600

h. The following arate experiments, each mone

procedures resulting

treatment (controls);

were performed in a total of 6-8

group. Rats were given or (2) daily injections

(oFSH, 20 U/mg; NIADDK-0FSH-17; SI) in PBS, pH 7.0, containing 0.09% PBS)

for

13 days

twice-daily

beginning

injections

Chemical

Co.,

controls Between

Results

of 0.5

St. Louis,

and 0800

half and

Day

MO)

horFSH

0.04 times NIH-LHpig skin gelatin (gel-

27 of age.

IU hCG

sepin

either (1) no of 2 pg ovine


. C

0 C C C

.0 (3

(0..

(0

2’.It)

N

X

-m

x >-o I..

(I).-

Oo >-

ma, 0 >. .C ‘5

C0. 00 0(0 .C

0.

(5

(0

0

-

FSH

AND

OVARIAN

CYSTS

IN THE

HYPOXD

153

RAT

11 04 II)

‘5

(0(5 0

u

.0 0

0

I

IS (5(0

0

N N

4’

-p I,

L1)I

.

fl 0#{149}

ISO

000

C

I”

15 C

0’5’5

C

(5

O,.? >N 0( -

X >-(5

0’5 a, C

E C

(J

.E C

0

.0

(0 (5

(0(0 15(5

154

BOGOVICH

range:

0.60

ries

mm2)

from

were

control

six times

HYPOXD

tively). Since neither thecal appeared stimulated for the 3B), the larger cross-sectional

did did

not not

have meet

cysts. In striking

contrast

ovaries

FSH

than

those

of ova-

dione values for HYPOXI) circles) displayed only

rats treated with sporadic increases

tissue rats (Fig. due to

values.

concentrations

antral follicles present in the thecal shells of these

ments.

(Fig.

3A and

2A,

nor stromal-mnterstitial FSH-treated HYPOXD areas seem primarily

the large number of atretic these ovaries. In addition, follicles follicles

larger

rats

small since

a stimulated the classic

appearance morphological

respec-

(Fig. 3B), criteria

the for

Androsteneclione

to all other +

in vivo

hCG-treated

treatment

groups,

rats

displayed

HYPOXD

Testosterone panel) were

for were

circles) Serum

ng/ml through

C and residual

trast,

by

cal shells markedly

(Fig. 3D), stimulated.

and In

the stromal-interstitial tissue addition, the cross-sectional

of ovaries from FSH + hCG-treated range: 1.76 mm2) was approximately ries from control licles were first

HYPOXD observed

37 of age,

agrees

which

In one hCG FSH

on

the

not

cysts

in response

precystic group on

with

HYPOXD

beginning on These animals after

(data

and

the

hCG

for

rats

were

this im-

given

Day 28, followed displayed cystic

Day

9 of combined

shown),

demonstrating

by fol-

gonadotrothat

to treatment with of the development

to combined

folDay

9-day

with cyst development progesterone-synchronized

ulation by LH-like activity prior hCG did not change the timing licular

well

experiment,

morning

treatment

Cystic treatment

remarkably

alone for 3 days, + hCG treatments.

licles pin

additional

HYPOXI) rats (30.7 mm2, 22 times that of ova-

animals. in this

treatment regimen associated dose of hCG in the intact mature rat [9].

was area

stimFSH + of fol-

gonadotropin

treat-

ment. Serum

Hormone

The

effects

individual

in vivo

treatment

regimens

on serum progesterone, androstenedione, testosterone, estradiol, estrone, and DHT are illustrated in Figure 4. Serum progesterone concentrations (Fig. 4, top left panel) were virtually imen with

undetectable save hCG

throughout

± 0.5 ng/ml) than treatment groups

serum

(