The neurohypophysial hormones

Animal Reproduction Science, 2 (1979) 43-56 0 Elsevier Scientific Publishing Company, Amsterdam - Printed in The Netherlands

THE NEUROHYPOPHYSIAL

MARY L. FORSLING,

43

HORMONES

A. A. MacDONALD

and F. ELLENDORFF

Department

of Physiology, Middlesex Hospital Medical School, London WlP 6DB, .. and Institut fur Tierzucht und Tierverhalten, 3057 Neustadt 1.

ABSTRACT Release animals

of oxytocin

including

essentially

similar

undetectable

and vasopressin

in all species

in late pregnancy

centrations

concentrations

neurohypophysial

hormones

release

vasopressin blood.

is confirmed

The mechanisms able interest to surround

the concentrations

underlying

the subject

believed

world

from which

myths

appear

they only emerged

has produced

underlying

parturition.

myometrial

activity

activity

appears

the aboriginal

literature,

in clinical

years

before

Whilst

contributed

the work of the

picture

of the changes

Estimates

of circulating

concentrations

dependent

on the development

influence change

to the cervix-dilating of posterior

Surprisingly

physiological designed

body of indirect to the changes

some

type

lobe to stimu-

(Dale, 1906) and by 1909 Blair Bell

practice.

studies

it was

some strange

they bring about the abrupt

of the extracts

recognised

consider-

has come

in which

of by their mother.

seen in pregnancy

The ability was early

A considerable

that oxytocin

myths

in

release.

have excited

inhabited

comprehensive

in which

to have been paid to the possible

performed.

children

into the scientific

contractions

had used the observation

was some twenty-five

of vasopressin

times and much mythology

of unborn

an increasingly

While

results

to the pti of the

These are in a large part the factors which

in labour.

late uterine

haemorrhage

of parturition

when dreamt

and the manner

from the spontaneous occur

as, for example,

that the spirits

in

of

is also descrite.l, data

being related

stimulus

since earliest

to have extended

past few years

which

the initiation

Secretion

being presented.

employed,

as an effective

and speculation

fetus

preparations

achieved

low or con-

little change

been noted.

and porcine

is

being

labour until maximum

Relatively

has

by the stimuli

The pattern

concentrations

during

of the fetus.

catheterised

in a number of domestic

is discussed.

oxytocin

of vasopressin

is unaffected

release,

Hypoxia

generally

studied,

in the ovine

from acute and chronically oxytocin

parturition

and increasing

are found with delivery

the circulating

during

the pig, sheep, goat and mare

role of oxytocin

and it

to look at this question

evidence

was produced

in parturition of oxytocin

of radioimmunoassay,

little attention

were

indicating

(Chard, 1977).

during

parturition

were not

as has been the case with

44 many

hormones

since sensitive

Application

1960's.

were markedly horses,

elevated

important

parturition

However,

during

the expulsive

in parturition

Relatively

parturition,

are stored

as markers

although

together

and are released

much

and maintenance The question

phase.

recently

a number

recently

"carrier

proteins"

in the neurosecretory

granules

hormones

(Legros,

1978).

on the anterior

RELEASE

demonstrated

of oxytocin

release

who,

of the rabbit mammary

found low levels of oxytocin

pregnancy.

Marked

of the placenta,

increases

were performed

similar

pattern

on parturient

of a sensitive although

in the jugular

parturition

obtained

accompanied

the finding

in the goat.

by bioassay

with

of the placenta,

suggest

Subsequently A

low concentrations concentrations

to the problem

confirmed

of at

concentrations

were of up

They also noted a good correlation

in pregnancy

Again

no

and early

labour

of 11 - 35 PU ml-l were found in the third stage. of the membranes

operation.

concentrations

that oxytocin

these

in these later studies

and radioitmnunoassay.

the delivery by Caesarian

that oxytocin

and on delivery

recorded.

and maximum

reported

stage of labour and 28 - 37 UU ml-l release

labour

in late

from the vulva.

in the plasma of mares

the fetus had been removed

of the superfused

goats and cows using bioassay.

radioimmunoassay

(Allen et al., 1973), but concentrations

delivery

and during

dilatation

the concentrations

was detectable

particular

the fetal

was

vein blood

Chard et al. (1970) found circulating

lower.

the results

oxytocin

and interest

based on the milk

gland and the response

horses,

the stage of cervical

to 142 VU ml-l during

second

parturition

using bioassays

of release was seen in these animals

during

Application

between

role in parturition.

at the time of birth.

were seen before

the time when the fetal head emerged

oxytocin

fetal

peak values of 150 - 1665 VU ml-l being

studies

relatively

has, of

which

lobes, although

in the sheep during

in 1961 by Fitzpatrick

response

observations

by some

A subject

in this respect

and intermediate

rat uterus,

oxytocin

been considered

OF OXYTOCIN

The pattern

ejection

so-called

is the possible

is well developed

of vasopressin have been made

has largely

system

has any

of observations

has been shown to be important

neurohypophysial

oxytocin

(Lincoln et al., 1977).

These

The fetal pituitary centred

including

as to whether

of whether

They have therefore

function

concentrations

species

of labour or is merely

on the release

concentrations.

the hormones.

interest

domestic

there is still some debate

with neurohypophysial

with

of neurohypophysial

excited

in several

have been performed

in neurophysin

since the early

that plasma oxytocin

is even raised on occasions

few studies

on the changes

course,

had been established

showed

plays a role in the initiation

function

during

during

cows and goats.

oxytocin

bioassays

of these assays

in the

Interestingly,

in mares

from which

These observations,

in

are elevated

the

is largely

during

concerned

with

45 expulsion

of uterine

Oxytocin polytocous animals

therefore

singletons

performed

most studies or twins.

catheters,

the miniature

pigs had bipolar

(Naaktgeboren

et al., 1973).

release

blood samples

for periods

lactation.

species

blood samples

of parturition,

A clear pattern

was seen in all animals,

2Or

during

16.5 1.1

on several expulsion

an example

(Haldar,

In

to record evidence

1970; Gibbens

and

determination. of two minutes,

days at the end of pregnancy,

of the fetus and subsequently

release,

being given

3.8 1.9 0121 In

of

from

vena cava.

each over an interval

of oxytocin

3.7 1.6 0.16

the pattern

is considerable

but in spurts

were collected,

were

in the uterus

were used for oxytocin

of a total of twenty minutes

at the beginning during

electrodes

in

on domestic

Blood was sampled

Since there

is not continuous

1976) integrated

Sequential

pig to determine

the tip lying in the superior

activity

that oxytocin

of fetuses

have been performed

at the time of parturition.

silastic

of the uterus.

delivery

A series of observations

addition

Chard,

involution

on the pig and miniature

of oxytocin

indwelling

and possibly

However,

species.

producing

release

contents

could also play a part in the ordered

similar

to that of other

in Fig. 1.

1.8 P (nglml) Ei (no/ml) 0.01 E; (r&ml) :.:.:.: ..:... ::: :’ :.

15 = E 3 z c

lo-

:.. a

i 5-

..:

;

:.;:i;

.,. .: .:.. :: .:.:

-

.:.: ,I, : j ,.:.. .:. ..

10.00-10.06 Lactation (+lday)

8.55-8.63 -5days

Fig. 1. Plasma oxytocin concentration in the miniature pig during late pregnancy, parturition and lactation. Determinations performed on plasma samples taken over two-minute intervals at the times of day indicated. Concurrent progesterone (P), oestrone (El) and oestradiol concentrations (E2) are also shown. Delivery of a fetus is indicated by the arrow.

Elevated

concentrations

parturition; olacenta.

maximum

of oxytocin

were first seen during

values were obtained

In those animals

in which

during

delivery

plasma oxytocin

the early stages of of the fetuses

was determined

and

at the birth

46 of a number

of fetuses,

concentrations

of oxytocin.

but much smaller parturition

it was seen that delivery

amounts

in terms of duration

(recorded

of total electrical

phases of electrical

coefficient

(0.93) was obtained

that there is a local positive

The fact that the plasma oxytocin throughout

of uterine

5

between

per hour.

seen initially

The highest

concentrations either

correlation

concentration

within

were closely

against

one to speculate the uterus.

related

that the relatively

were sufficient

in

hr-l) or the number

operating

concentrations

lactation,

expressed

(Fig. 2) leading

mechanism

the course of labour suggested

of oxytocin

oxytocin

(seconds

of contractions

feedback

during

by M. A. M. Taverne)

activity

activity

with very similar

release was effective

with a plot of log oxytocin

the square root of the frequency

activity

was maintained

That oxytocin

by the good correlation

activity

of distinct

concentrations

secretion

were released.

was indicated

and the electromyograph

Hormone

was achieved

to uterine low

for the maintenance

activity.

.

r =0.93

.

.

. .

. 0.

.

.

.

. .

.

Fig. 2. Relationship of plasma oxytocin and uterine activity expressed as frequency (number of bursts of electrical activity per hour). EMG data provided by Dr. M. A. M. Taverne from experiments on 7 animals. Since there are complex would

be simplistic

causing

oxytocin

inter-related

factors

operating

during

parturition

to state that any one single factor was responsible

release.

However,

it does appear

that stimulation

for

of stretch

it

47 receptors

in the cervix

down following

vaginal

is the prime distention,

stimulus

the Ferguson

1969) and it has now been shown by direct with bioassay

(Roberts

that vaginal

distention

circulating secretion

oxytocin

which

Roberts,

could be blocked

vaginal

Oestrogen during

are dependent

The ovarian

of oxytocin

release

progesterone,

A similar

complex

of oxytocin

of prostaglandin not appear induced

relationship or release

release. concentrations

changes,

they are

In addition to

et al., 1979).

exists

between

of endogenous

into the uterine

venous

affects

the uterine

B-mimetic

as a similar

drugs.

result

sensi-

release

oxytocin

release

that prostaglandin

infusion

could stimulate

intramuscular

injections

four miniature dioestrus. animals. initial

similar

of prostaglandin increase

concentrations

(Fig. 3).

The response

appeared

sows before

concentrations

injection

uterine

in 1972

in the human,

so to on

sows during

with both groups

low or undetectable

prostaglandin

of during

an

into the neck muscle injection

there was a

of 13.4 t 1.8 JJU ml-l in the Landrace

and unrelated

in that there was little

which were

are blocked

The study was performed

an injection

for oxytocin

injection

oxytocin-

the response

and five Landrace

peak concentrations

to be specific

prostaglandin

Fza.

This does

Prostaglandins

et al. showed

release

sows and 9.7 + 2.2 UU ml-l

with prostaglandin

vasopressin

oxytocin

remained

After

in plasma oxytocin,

being seen in the miniature

Brummer

results were obtained

period and following

diluent

stimulate

on the pig to determine

of 5 mg prostaglandin

Plasma oxytocin 60 min control

associated

directly.

sows six days after farrowing

Essentially

thus released

in turn could be enhanced.

have now been performed

the release

(Flint et al., 1975).

being forced out during

may also stimulate

observations

and oxytocin.

stimulates

is seen if the contractions

If the prostaglandins

then oxytocin

prostaglandins

oxytocin

blood

to be a result of prostaglandins

contractions

contractions

plasma

of oestrogen

inhibiting

on the oxytocin

of course,

to

1968;

following

concentrations

effect

(Forsling

are thought

and Share,

released

and progesterone

in the pig of the hormone

to oxytocin.

Infusion

sharp

steroids

in the pig but, in common with many other

oxytocin

in the

anaesthesia

Release

(Roberts

on the background

to the fall in progesterone

influencing tivity

(Flint et al., 1975)

area.

and Share

potentiating

(Folley,

in plasma

increase

by lumbar epidural

does not seem to have an immediate

parturition

related

Roberts

let

it was shown that oxytocin

surface

1975) have shown that the amounts

oestrogen

is well known

reflex could well be significant

by a number of hormones.

distention

Milk

of oxytocin

by a brisk

In addition

The Ferguson

in this respect.

and progesterone;

release.

1968) and radioimmunoassay

has a long cervix with a considerable

is also modulated

reflex,

determination

in the sheep is followed

in this situation

be significant

with

and Share,

concentration.

(Flint et al., 1978).

for oxytocin

1.8 + 0.38 PU ml-l

and 2.6 + 0.3 VU ml-l after.

(S.E.M.

sows.

to the stress change

in the

in the Landrace It remains

to

48 be established Should

if this effect

this prove

positive

of prostaglandin

to be the case, it would

feedback

mechanism

operating

provide

during

MINIATUREPIGS PGF SAL ; 2-

is of physiological an additional

significance. example

of a

parturition.

SAL

PGF ;2-

I

I_:\-.....

50

0

SAL I

PGF 12= I

SAL I I

150

liJ0

200

PGF2.c I

250 TIME (MINS)

in the miniature pig after prostaglandin Fig. 3. Plasma oxytocin concentrations Injections of saline and prostaglandin Fzcr (PGF2,) were given at the injection. times indicated by the dotted lines.

VASOPRESSIN Since,

under most

in stimulating vasopressin

uterine

release

but the increases In a limited

circumstances, activity,

during

in circulating

study

in the mare

24 PU ml ml being reported chronically elevated

catheterised

release

the latter

fewer studies

concentrations

release associated

have been performed in a number

it was found that vasopressin phase,

a maximum

it was found that vasopressin during

is of some physiological

is the case is suggested

concentration

parturition.

by the observation

were

the highest

It is not clear

value or represents

late pregnancy

like of

study on the

concentrations

the last week of gestation,

with stress during

on

of species,

concentrations,

In a more extensive

(Allen et al., 1973). sheep

than oxytocin

are less than those of oxytocin.

being noted in the 48 hours before

if this augmented specific

is less effective

It is stimulated

in the expulsive

in four of six animals

concentrations

relatively

parturition.

could be elevated

oxytocin,

vasopressin

non-

and delivery.

in the Landrace

That

pig that

49 vasopressin were

concentrations

low with

small bursts Secretion

4.2 VU ml-l. labour

were unrelated

(Forsling,

of secretory

of vasopressin

unpublished

to oxytocin

activity

The values

concentrations.

giving

increases

is also unaltered

of up to

in the goat during

observations).

NEUROPHYSINS Neurophysins release would

are released

the hormones.

therefore

neurophysin

Any changes

directed

against

followed

those of oxytocin

bovine

specific

neurophysin

in other

animals

studied

assays

Prepartum

lay within

Neurophysin

oxytocin. exceeded

concentrations

the release

neurophysin

of bovine

and neurophysin

closely

neurophysin

I

increases

of neurophysin Sporadic

for

I in the ten increases

were made

were in

in this investigation,

that the percent

increases

less than those generally

in the studies

The

of up to 20 ng ml-l occurring

of oxytocin it appears

I

II with vasopressin.

to that just described

concentrations

were relatively

I levels

and

for neurophysin

Legros et al. (1977) using

the range 0.5 - 1.4 ng ml-l.

No determinations

assays

to

parturition

of oxytocin

in plasma

I release was very similar

but from the data of other workers, neurophysin

during

known

In this species release of neurophysin

with oxytocin

species.

stage.

secretion

et al., 1972).

have followed

seen in the first stage with greater the second

stimuli

determinations

Changes

(McNeilly

and after parturition.

of neurophysin

oxytocin

following

in the goat using heterologous

neurophysins.

is said to be associated pattern

in neurophysin

Parallel

be of interest.

have been made

and II during

into the circulation

in

seen for

of Legros et al. generally

II but release of this first peptide was stimulated.

those of neurophysin

THE FETAL NEUROHYPOPHYSIS While

it thus appears

unlikely

a role in the initiation hypophysis

cannot

the presence

presence

of oxytocin

increase Pearson

by Silverman rapidly

factor

not been described Neurophysin (Alexander

and Kay (1953).

neurosecretory

of many

The hormone

in other

content

species,

such a factor

and

The developpig has been

is known to

1972), and the work of

system.

of a

Although

it has

could well be present.

in fetal sheep pituitaries

et al., 1973) and Chauvet

by

species

that this is due to the production

in the fetal hypothalamohypophysial

was first demonstrated

pig.

system of the fetal guinea

(Burton and Forsling,

The

was established

Both vasopressin

in the fetal pituitaries

et al. (1975) has suggested

stimulatory

of parturition.

in the fetal hypothalamus

of Benirschke

birth

play

of the fetal sheep and even suggested

to the control

(1975) in some detail.

before

hormones

from the fetal neuro-

1977), most data being from the rat and the guinea

ment of the hypothalamic studied

material

have now been demonstrated

(Forsling,

, a contribution

in the pituitary

studies

neurohypophysial

As long ago as 1937 Bell and Robson demonstrated

could contribute

of neurosecretory

the histochemical oxytocin

of parturition

be ruled out.

that the fetal hormone

that maternal

in 1971

et al. (1976) have now isolated

neurophysins

50 from the fetal bovine pituitary MSEL-neurophysin+,

the peptide

that in the adult.

This neurophysin

than the VLDV-neurophysin+, the fetus vasopressin A report which gations

excited

in the pituitary

and Fisher,

quantities

1977).

are present

vasotocin

release

concentration

the normal

does have oxytocic

of hormone

chronically

activity,

catheterised

and vasopressin

ovine fetus

1976;

at birth and it (Swaab et al.,

even though 1968).

content

suggesting

Direct

of vaso-

that considerable

of labour

it has been Some authors

of the neurohypophysis

that there

determination

is, of course,

in fetal plasma

of oxytocin

of arginine

and Perks,

(Berde and Boissonnas,

a fall in the hormone

that in

than oxytocin.

The percentage

course

with

amounts

a series of investi-

(Vizsolyi

been suggested

at the time of parturition.

but concentrations

quantities

and initiated

(Froger et al., 1976),

at the time of delivery

the observation

in the rat fetal pituitary

promotes

have been able to demonstrate

in greater

(1969) on the presence

It has however

to be 25% that of oxytocin

hormone

with

greater

of fetal sheep and seals.

1977).

of vasotocin

Arginine

is consistent

interest

was identical

to be present

in relatively

and Perks

that the fetal

with vasopressin,

falls as term approaches

is this fetal factor which

reported

They deduced

appeared

considerable

tocin in the pituitaries Skowsky

which

is present

was that of Viszolyi

vasotocin

gland.

associated

is fetal

of circulating

required

to confirm

have been followed

this,

in the

in late pregnancy.

OXYTOCIN Although

Alexander

considerable

term - 147 days), exteriorised

did appear

Forsling

catheterised

cortisol

Oxytocin

is known to be rapidly

is also accompanied of neurophysin release

It

exteriorised

fetus,

except

(Forsling

in the plasma

et al., 1971) which

to detect

The hormone

parturition,

rapidly

oxytocin however

at a time

The highest

concen-

afterwards.

et al., 1975b).

concentration

is generally

is the stimulus

to obtain oxytocin

in response

(full

in the fetus with a half time of dis-

is not clear what

et al. (1976) failed

failed

increasing.

and fell away quite

cleared

in

in the plasma of

in late pregnancy.

were

of 2.5 min

by an increase

I (Robinson

of oxytocin.

Alexander

at delivery

from the circulation

oxytocin

in the 50 hours preceding

were obtained

was present

from 80 days gestation

et al. (1975a) similarly

concentrations

trations

appearance

to detect

sheep fetuses

in the circulation

the plasma

that oxytocin

in fetal sheep pituitaries

they were unable

fetuses.

in chronically

when

et al. (1974) reported

quantities

to infusion

release

Delivery

in the fetal calf

associated

with the

for oxytocin

release.

in the acutely

of calcium

chloride

and even

' Chauvet and Acher have proposed a classification of neurophysins based on the composition of the N-terminal sequence. Hence MSEL-neurophysin (Ala Met Ser Asp Leu Glu Leu Arg) and VLDV-neurophysin (Ala Val Leu Asp Leu Asp Val Arg).

51

then the response

sheep placenta uterine

could

is impermeable

activity

when infused

Consideration

It is possible

was inconsistent.

at the time of parturition

influence

to oxytocin

uterine (Forsling

into the fetus

of fetal oxytocin

Landrace

were studied

released

for although

et al., 1975b)

(Nathanielsz

has now been extended

fetal pigs from ten sows of the German known and three or four fetuses

that fetal oxytocin activity,

the

it can increase

et al., 1973). to the pig; in eleven

breed the gestational

age was

at each of three ages of gestation;

80 - 84 days, 95 - 100 days and 110 - 114 days, full term in this breed being 114 days.

Blood

chronically

samples were collected

implanted

in the jugular

for oxytocin

vein of both mother

were allowed

three to ten days to recover

observations

were made.

fetuses

then haemorrhaged

for ten minutes.

Control

blood

samples were collected

were obtained

after the start of the haemorrhage

and a second

Oxytocin

was present

in low concentrations

maternal

plasma over the time studied

identical

or undetectable

as shown in Fig. 4.

The animals

operation initially

blood volume

from mother

from catheters

and fetus.

from the implantation

at a rate of 1.5% estimated

Blood samples

determination

per minute

and fetus 30 minutes haemorrhage

performed.

in both fetal and Haemorrhage

failed

RESTING HAEMORRHAGE

MATERNAL

FETAL

5 +

Fig. 4. and after Landrace limit of

before

and

Concentrations of oxytocin in fetal and maternal plasma before fetal haemorrhage. Experiments performed on sows of the German breed. The horizontal line at 1 nU ml-l indicates the lower detection of the assay.

to

52 elicit

any change

appeared

in the circulating

to be no increase

parturition.

in the circulating

It is possible

therefore

give birth to a large number fetal oxytocin

which

concentrations.

concentrations

that in animals

of offspring,

is important

Unlike

the sheep there immediately

before

such as the pig which

it is the maternal

rather

than the

in parturition.

VASOPRESSIN Vasopressin chronically

catheterised

ised fetuses term

concentrations

delivery

sheep fetus.

et al., 1971).

was undetectable

(Alexander

Similarly,

shown to be elevated

during

(Stark et al., 1977). stimuli

for vasopressin

the response pressin

release

vasopressin

release.

in the adult.

et al., 1973; Alexander in causing

vasopressin

et al., 1972).

release

in the acutely

ewes of gestational

for vasopressin

the rise in plasma

pronounced, afferent

suggesting

fibres

acidaemia

were,

The resting studies contrast

than in the sow.

produced

the magnitude was above

(Alexander

Increases

in nitrogen

in vasopressin

The stimulus

was

Release

involves

vasopressin

catheter-

being significantly in vagotomised

peripheral episodes

related

sheep was less

receptors

whose

of hypoxaemia

with raised vasopressin were also determined

above and the response

to stimuli

concentrations

in pH.

concentration

the plasma

levels.

In

in the fetus blood

of vasopressin,

In all but two animals

and in these animals

and

in the

noted.

of 15% and 30% of the estimated

in the circulating

to the change

7.39 after haemorrhage

fetus

in the chronically

Spontaneous

Haemorrhages

in response (Skowsky

10% oxygen

in neurophysin.

of lysine vasopressin

small increases

being related

exteriorised

found to be associated

to the sheep the unstimulated

were higher volume

that the response

concentrations

may be augmented

in ACTH were also demonstrated.

hypoxia.

on the fetal pig described

for both

being related

was also shown to be effective

concentrations

run in the vagus nerve. in addition,

to be effective

experiments

in plasma osmolality

these observations

hormone

to the fall in pH and Pa02 during

of vaso-

age 100 - 104 days.

as increases

possible

were made on

stimulus

by administering

by an increase

(1978) was able to confirm

ised sheep,

secretion

Hypoxia

was provided

were accompanied

not specific Rurak

Vasopressin

have been as well

to identify

observations

was found

such as increases

et al., 1976).

The stimulus

to anaesthetised concentration

stimuli

animals

concentrations

parturition

have been made

in individual

towards

concentrations

Some of the earliest

increases

in exterior-

catheterised

highest

vasopressin

This manoeuvre

and ACTH release,

physiological

Plasma

and

until 48 hours before

since this is known to be a potent

to the fall in blood pressure. to more

of samples

adrenocorticotrophin-induced

A number of attempts

to haemorrhage

was undetectable

As with oxytocin,

were seen at the time of delivery.

exposed

in a number of fetuses

in chronically

in the majority

et al., 1974).

in the acutely

Vasopressin

of 90 - 107 days, but was detected

(Alexander

vasopressin

have been determined

the pH

vasopressin

53 concentrations which

increased

the final

and 20.3 11lJml-l

respectively.

subjected

to hypoxia

effective

stimulus

increasing

up to values of 6.5 VU ml-l.

the umbilical

of vasopressin

release,

(+ S.E.M.,

cord.

fluid balance, causing

vasopressin fetus

concentrations

again flow could

produced

serve to produce for oxytocin,

to vasopressin an indirect

of 90 days

of 101 - 102

effect

is rendered

studies

in the fetus are required of the hormone

in the

It could blood

circulation.

it

AS impermeable

it could produce

fetal ACTH

release

at

likely by the recent

are found

of the factors

concen-

placental

However,

influence

to

Alternatively,

to be effectively

1978).

the more

peptides

together

vasopressin

of speculation.

if it reduced

appears

on the uterus or possibly

More detailed

eminence.

of increased

et al., 1973; Rurak,

that neurohypophysial

in blood pressure

in the umbilical

the sheep placenta

that infused

that it could contribute

could be affected.

vasoconstriction

(Alexander

increase

For example,

of the amniotic

The observation

is also a matter

production

This last possibility

observation

actions

greater

The function

control.

hormone

the permeability

1978) suggests

(Rurak,

act on the blood vessels. then placental

term.

in fetuses

and of 111 - 113 days from

from the mother.

at the time of parturition

reported

to tk a very

is not known, but it could

affecting

a significantly

cardiovascular

trations

in the fetal animal for example

uptake of water

than in the adult

normal

were 8.2

(n=19) to 60.2 2 7.7 PU ml-l.

The role of vasopressin

membrane,

This proved

n=5) to 40.9 + 9.7 VU ml-l;

days from 10.4 + 1.6 (n=12) to 61.6 + 12.5 VU ml-l;

influence

concentrations

In a series of acute studies the fetuses were

by clamping

from 7.8 + 0.72

16.7 + 1.69

In those two animals in

pH was less than 7.38 the vasopressin

in the region of the median

controlling

with a comprehensive

vasopressin

investigation

secretion

of the

in utero.

ACKNOWLEDGEMENTS The skillful

technical

and the financial

assistance

support

of U. Bierman

from Deutsche

is gratefully

acknowledged

Forschungsgemeinschaft.

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