GENERAL

AND

COMPARBTIVE

Temporal

ENDOCRINOLOGY

Synergism

SUPPLEMENT

of

Prolactin

ALBERT
Department

oj

Zoology

and

Baton

3, 499-508

and

(1972)

Adrenal

Steroid9

I!. MEIER

Physiology,
Rouge,
La.

Lowkiaza
YO808

State

University,

Many
responses to prolactin vary with a periodicity of 24 hr. The daily variations are entrained by the photoperiod and mediated by adrenal steroids. The temporal relations between these hormones are thought to control and coordinate many
physiological
conditions in vertebrates, in&din g some involved in developmental
and seasonal changes.

Time is a critical dimension in the organization of living systems. The principal

unit of biological time measurement, the
circadian or daily rhythm, is present at
all levels of organization.
Although
the
rhythms may persist under constant conditions of light, the photoperiod is the primary environmental
entraining
agent or
synchronizer of the rhythms among vertebrates. As the cell is the basic unit in terms
of space and matter, so it is also the repository of the circadian rhythm. The organization of the individual cellular rhythms
for the construction of organismal rhythms,
and the mediation of photoperiodic entrainment of the circadian rhythms might well
be important
functions of the endocrine
system.
Daily rhythms have been reported for
many hormones, including adrenal steroids
(review, Halberg,
1969) and prolactin
(Clark and Baker, 1964; Kent, Turnbull,
and Kirby, 1964; Meier, Burns and Dusseau, 1969) ~ Although
correlations have
been made between hormone rhythms and
other rhythms, there is little direct evidence that the time of the daily presence
or peak level of hormones has important
physiological relevance. The special task
of our laboratory during the last several

years was to investigate the functions oE

daily hormone rhythms, particularly
with
regard to prolactin and the adrenal steroids.
DAILY
VARIATIONS
RESPONSES
TO

The metabolic
role of prolactin
was
demonstrated in the pigeon 30 years ago
(Schooley, Riddle and Bates, 1941). The
loss of body weight in hypophysectomized
juvenile pigeon was inhibited by prolaetin
injections.
Prolactin
also promoted
increased food consumption and stimulated
splanchnomegaly. These findings were confirmed in a later study (Bates, NIiller and
Garrison, 1962).
In the whitme-crowned sparrow, Zonotrichia leucophrvs gambelii, prolaetin injections made during the intermigratory
periods caused increases in body weight
and fat. stores that are equivalent to those
found during the migratory seasona when
this passerine migrant is nat,urally heavy
with fat (Meier and Farner, 1964). These
results were duplicated in another migrant,
the white-throated
sparrow; Zonotrichiu
albicollis (Meier and Davis, 1967). In addition, it was found that the time of da>r
when the injections are made is critically
important. Injections at midday of a 16-hr
daily

The studies reported herein were supported by

funds from the National
Science Foundation
(Grant. No. GB-20913) and from the U. S. Public
Health Service (Grant No. 5 RO 1 AM 13400).
Recipient
of a Public Health Service Research
Career Development
Award, GM-17,898.
Press, Inc.

photoperiod

elicited

large

g;aine

in

body fat levels, whereas injections given

early in the photoperiod caused losses in
fat stores.
Since the initial discovery in the whitethroaied sparrow (Meier and Davis, 19671,
499

@ 1972 by Academic

IN FATTENING
PROLACTIK

500

ALBERT

H.

daily variations in fattening responses to

prolactin have been found in 3 teleost
fishes, 1 amphibian, 2 reptiles and 1 bird in
addition to the white-throated
sparrow (see
Table I for references). In general, the interval of fattening
response to prolactin
occurs about midday of 16-hr photoperiods.
The effect of length of photoperiod on the
time of the fattening response interval was
examined in the Gulf killifish, Fundulus
grandis (Joseph and Meier, 1971). When
prolactin was injected at 0, 4, 8, 12 or
16 hr after the onset of light, the peak
fattening response resulted from injections
at the 8th hr regardless of whether the
length of the photoperiod was 8, 12 or 16
hr (Fig. 1).
Animals that fatten in response to prola&in also consume more food than those
that do not fatten. Goodridge and Ball
(1967) believe that the fattening effect is
mediated by the hypothalamic
appetite
centers inasmuch as prolactin did not induce lipogenesis in pigeons on a limited
diet. However, the daily fattening response
r-

FIG. 1. Daily variations

in fattening
responses
to
prolactin
in Funchlus grandis
held on 3 different
photoperiods
and injected
daily for 6 days at 0, 4,8,
12, or 16 hr after the onset of light. Before treatment,
the percent
lipid
of the dried
carcass
averaged
6.71 * 0.51 and the percent
lipid of the dried liver
averaged 30.02 f 3.23. (Josephand Meier, 1971.)

MEIER

to prolactin is present in the golden topminnow, Fundulus chrysotus, even when

food is withheld for several days prior to,
and during, the experimental
treatment
(Meier, 1969a). Increased fat stores are
stimulated at the expense of other tissues
in the body. The increased appetite that
accompanies fattening certainly serves to
support lipogenesis ; however, the increased
appetite appears to be a consequence of
fattening in the golden topminnow rather
than a primary inducer.
In the pigeon, the principal site of lipogenesis is the liver (Goodridge and Ball,
1967). Although prolactin alters the metabolic traffic in the liver, suggesting a lipogenic effect when the injections are in
uiuo, the effect is not present when prolactin
is added to in vitro preparations. Apparently, the fattening effect of prolactin is
either mediated by another factor or dependent on synergistic factors.
DAILY VARIATIONS IN A VARIETY OF
RESPONSES TO PROLACTIN
Daily variations in responses to prolactin
are by no means limited to the fattening
response (see Table I). Many of the wellknown effects of prolactin vary markedly
during the day. One of the more noteworthy daily variations
is that of the
pigeon cropsac which has served as the
basis of prolactin assays for about 40 years
(Riddle, Bates and Dykshorn, 1932). Prolactin injections given early during a 12-hr
photoperiod have little effect compared to
injections given later in the day (Burns
and Meier, 1971; Meier, Burns, Davis and
John, 1971). The daily rhythm of cropsac
sensitivity is present whether the injections
are given locally (intradermal)
over the
cropsac or systemically (intramuscular).
Another effect of prolactin is the inhibition
of frog tadpole metamorphosis
(Etkin and Gona, 1967). Examination
of
the possibility of a daily rhythm of effectiveness revealed that prolactin can inhibit
completely the progress of metamorphosis
in Rana pipien.s tadpoles at certain times
of day but that it is ineffective at other
times (Breaux and Meier, 1971). Our results suggest the possibility that prolactin

TEMPORAL

SYNERGISM

TABLE

501

DATLY VARIATIONS IN RESPONSES TO PROLACTIX

Response

Reference

Species
__-

__Body

Fat, Gain

No;l-lipid
Locomotor
Antigonadal

or Loss

Growth
Activity
Effect,

Inhibition
of Metamorphosis
Eft Water
Drive
Cropsac
Stimulation

Fundulus
chrysotus
Fundul~us
grandis
Fund&s
kansae
Rana pip&s
Anolis
carol&en&
Xantusia
henshawi
Zonotrichia
albricollis
Fun&us
chrysotus
Zonotrichia
albicollis
Zonotrichia

albiwllis

Passer domesticus
Rana pipiens
Notophthalmus
viridescens
Columba
livia

stimulates growth of the tadpole and inhibition of metamorphosis during the early
stages of the life cycle. As the phase angle
of the release of pituitary prolactin shifts
with respect to the photoperiod, the animal
matures and is permitted to metamorphose.
In this connection, the red eft water drive
of the spotted newt, Notophthalmus
viridescens, is also subject to marked daily
variations in responses to prolactin (Meier,
Garcia, and Joseph, 1971).
No&rnal
locomotor
activity
is considered a reasonably reliable indicator of
readiness to migrate in many nocturnal
migratory
birds. Prolactin injections can
induce nocturnal
activity
in the whitecrowned sparrow (Meier, Farner, and King,
1965) and the white-throated
sparrow
(Meier, 1969a) during the intermigratory
periods when nocturnal activity is generally
absent. In the white-throated
sparrow, it
was further demonstrated that only injections given during the afternoon hours in
late winter could elicit nocturnal activity
as well as increases in fat stores. Injections
given early in t,he day did not stimulate
nocturnal activity nor fattening.
Several other daily variations
in responses to prolactin have been found and
otthers are under investigation. The many
functions of prolactin clearly support the
rqntention of Riddle (1963) that prolactin

Lee and Meier,

1967; Meier,
1969
Joseph
and Meier,
1971
Mehrle
and Fleming,
1970
Meier,
1969a
Meier,
1969a
Trobec,
unpublished
Meier
and Davis,
1967
Lee and Meier,
1967
Meier,
1969a
Meier,
1969b
Dusseau
and Meier,
unpublished
Breaux
and Meier,
1971
Meier,
Garcia,
and Joseph,
1971
Burns
and Meier,
1971; Meier,
Burns,
Davis,
and John,
1971

is a generalized tropic hormone. We would

add that the specific functions of prolactin
depend on its temporal relations. Another
important daily response to prolaetin, rhe
antigonadal effect; will be discussed in a
later section.
CIRCADIAN
RESPOKSES

VARIATIONS
TO PRQLACTIK

IN

The daily variations in the responses to

prolactin are normally entrained by the
daily photoperiod. However, they are eircadian in that the rhythms persist in same
animals maintained
in continuous light.
Although the time of day when the peaks
occur are altered, both the rhythms of fattening responses and the rhythm of eropsac
response persist for about 12 days in the
common pigeon, CTolu?r&a livin, maintained
in continuous
light
(John, Meier, and
Bryant, 1972). Circadian rhythms of fattening responses also persist for at least
10 days in the Gulf killifish maintained
in continuous light (Meier, Trohee, Joseph
and *John, 1971).
ENTRAINMENT
RHYTHMS

OF THE
RESPONSE
TO PROLACTIN

The discoveries of a wide diversity of

daily responses to prolactin enabled us tro
make two basic conclusions: 1) the daily
variations in responses must be the results

502

ALBERT

H.

of another system that has a circadian expression, and 2) the diversity of responses
suggests that the entraining system affects
many, if not all, parts of the vertebrate
body. With these considerations, there are
relatively few possible systems that call
for investigation.
We have investigated the thyroid and interrenal hormones as possible entrainers of
daily responses to prolactin. Both groups
of hormones have diverse activities. In addition, the plasma and glandular levels of
both thyroid-stimulating
hormone (Bakke
and Lawrence, 1965; Singh, Ponda, Anderson, and Turner, 1967) as well as ACTH
and the adrenal steroids (review, Halberg,
1969) have been shown to vary during the
day.
In two teleost fishes, both thyroxin
(Meier, 1970) and hydrocortisone (Meier,
Trobec, Joseph and John, 1971) (Figs. 2
and 3) phase or entrain rhythms of fattening responses to prolactin. In these experiments, the entraining hormones were
injected at 1 of 2 different times of day
12 hr apart for 2 days only. After skipping a day following the injections of the
entraining hormones, daily injections of
prolactin were made for several days at
1 of 4 different times of day. Daily rhythms
of fattening responses to prolactin were
found in all the experimental groups. In

MEIER

$ 35
3o
:
0
Prolactin

.IL

IILL

lnjectlon

FIG. 2. Hydrocortisone
entrains
a circadian
liver
fat response
to prolactin
in Fund&s grandis
maintained
in continuous
light.
Hydrocortisone
(H) or
saline (8) were injected
at 0600 or 1800 on Days
1
and 3. Prolactin
was injected
daily from Day 5-11.
(Derived
from
Meier,
Trobec,
Joseph
and John,
1991.)

addition, this method allowed us to determine whether the daily variations in fat
content resulted from the actual time of
day when the injections were made or
whether they were entrained by the injections of thyroxin and hydrocortisone. It
is clear that the rhythms are entrained by
the injections of thyroxin and hydrocortisone rather than by some unknown factor
influencing tissue responses at specific times
of day (see Fig. 2). These experiments also

Prolactin

Fat Gain

Prolactln

12

FIG.

3. Temporal
summarizes

synergism
the results

of prolactin
of individual

Fat

Loss

12

Time
figure

12

(Hours)

and adrenocortical
hormones
experiments
on the Gulf killiiish,

(ACH)
green

controlling
fat levels.
The
anole, and common
pigeon.

TEMPORAL

illustrate that, the rhythms that are entrained by thyroxin or hydrocortisone may
persist for as long as 10 days under conditions of continuous light without
continued injections.
Although thyroxin alters the amplitudes
and the lengths of the free running circadian rhythms of fattening and cropsac
responses to prolactin in pigeons, it does
not entrain the rhythms as it. does in fishes
(John, Meier, and Bryant, 1972). On the
other hand, adrenal steroids do entrain
daily rhythms of fattening responses to prolactin in a variety of vertebrate species (see
Fig. 3) including 2 teleost fishes, 2 lizards,
2 birds and 1 mammal (see Table 2 for
listing and references).
ENTRAINMENT
TENISG
SPONSES

AND
IN

OF DAILY
FATCROPSAC
RETHE
PIGEON

It is possible in the pigeon to compare

the rhythms of two types of responses to
prolactin.
Both the fattening
response
rhythms and the cropsac response rhythm
are entrained by intramuscular
injections
of corticosterone
(Meier, Trobec, Joseph
and John, 1971). The peak fattening responses (abdominal fat, liver fat and intestinal weight) occur at 0 (or 24) hr after
eorticosterone
whereas the peak cropsac
response occurs 18 hr after corticosterone.

DAILY

I~ESPONSES

Fat

Locomotor
Reproductive

Gain

Species
or Loss

Activity
Sensitivity

Eft Water
Drive
Cropsac
Stimulation

Columba
livia
Mus muse&us
Zonotrichia
albicollis
Zonotrichia
albicollis
domesticus

Notophthalmus
Columba
livia

BY ADRENAL

STEROIDS
Reference

Fund&s
chrysotus
Fund&us
grandis
Anolis
carolinensis
Xantusis
henshawi
Zonotrichia
albicollis

Passer

The troughs of the rhythms of fattemng

responses are at 6 hr aft,er eorticosterone
and the trough of the cropsae rhythm is
12 hr after corticosterone.
The variations in timing of the rhythms
allow prolactin to stimulate either cropsac
proliferation
or fattening with gradations
between them depending
on prolactins
temporal relations with corticosterone. If
the times of the daily release of pituitary
prolactin and/or the rise in plasma eorticosterone vary in the pigeon as they do
in the white-throated
sparrow
(Meier,
Burns and Dusseau, 1969 ; Dusseau and
Meier, 1971), it seems possible that the
daily release of pituitary
prolact~in could
occur during a period of cropsac insensitivity resulting in little or no cropsac
proliferation.
Thus, prolactin might stimulate fattening at one time in the life cycie
of the pigeon and cropsac proliferation
at
another. Such a temporal reiaConship with
corticosterone might account for the findings of Schooley and Riddle (1938) with
respect to prolactin in pigeons of several
ages. On the basis of histoiogical observations and assays of pituitary
proh~tin,
they concluded that. the activity and concentration
of pituitary
prolactin
are as
great in immature pigeons (which are reietively fat) as they are durmg cropsac
enlargement in adult incubating birds.

TABLE
2
TO PROLACTIN
ENTRAINED

Responses
Body

SYNERGISM

viridescens

Joseph
and Meier,
unpublished
Meier,
Trobec,
Joseph,
and John,
Meier,
Trobec,
Joseph,
and John,
Trobec,
unpublished
Meier and Martin,
1971; Meier,
Martin
and MacGregor,
1971
Meier,
Trobec,
Joseph,
and John,
Joseph
and Meier,
unpublished
Martin
and Meier,
submitted
Meier,
Martin,
and MacGregor,
1971
Meier,
Martin,
and MacGregor,
1971
Meier,
Garcia,
and Joseph,
1971
Meier,
Trobec,
Joseph
and John,

1971
1971

1971

1971

504

ALBERT

The question of whether or not the entraining

activities
of corticosterone
are
directly on the mucosal tissues of the
cropsac was investigated using intradermal
injections of hormones over the cropsac
(Meier, John, and Joseph, 1971). Intradermal injections of corticosterone affect
the cropsac mucosa directly causing a daily
variation in cropsac sensitivity to prolactin.
Peak sensitivity
occurs between 12 and
18 hr after corticosterone, and least sensitivity occurs O-6 hr after corticosterone.
At the time of the trough, there is little if
any cropsac response to prolactin.
THE TEMPORAL
SYNERGISM
OF CORTICOSTERONE
AND PROLACTIN
IN THE
WHITE-THROATED
SPARROW

The functions of the hormone rhythms

might best be illustrated
by examining
their relations in detail in a single species.
The white-throated
sparrow, Zonotrichia
albicollis, is a nocturnal
migrant which
breeds in northern
North America and
winters in the southern United States (see
Wolfson, 1959; Helms, 1968). Spring and
autumn
migration
are accompanied
by
large body fat stores that provide an efficient energy source for flight. Reproductive development
occurs in the spring
reaching full maturation
after the birds
reach the breeding grounds. Following the
breeding season, the reproductive apparatus
regresses and the gonads remain small until
the following spring.
Since Rowans initial discoveries (1926))
many workers have demonstrated that day
length has an important role in regulating
metabolic,
behavioral,
and reproductive
events in the annual cycle of birds (reviews, King and Farner, 1965; Lofts and
Murton,
1968). Increasing day length in
spring is thought to stimulate fattening,
migratory behavior, and gonadal development. Recent studies in several birds have
demonstrated
that circadian systems are
involved in the photoperiodic
stimulation
of the reproductive system (Hamner, 1963,
1964; Farner, 1965 ; Wolfson, 1965 ; Follett and Sharp, 1969).
Although either naturally increasing day
lengths or .-artificially
increased photo-

H.

MEIER

periods in winter and spring may cause

changes associated with migration and reproduction, these conditions are not maintained indefinitely
by long daily photoperiods. Many
birds become refractory
within several months: the gonads regress,
the body fat is depleted, and nocturnal
activity ceases in nocturnal migrants.
A role of prolactin in controlling migratory fattening (Meier and Farner, 1964)
and migratory restlessness (Meier, Farner
and King, 1965) was demonstrated in the
white-crowned
sparrow, Zonotrichia
leucophrys gambelii. These results were duplicated in the white-throated
sparrow. In
addition, it was found that prolactin stimulated fattening (Meier and Davis, 1967)
and nocturnal activity (Meier, 1969a) only
when injected at specific times of day. In
general, prolactin was stimulatory
during
the afternoon
and inhibitory
during the
morning in a 14-16 hr daily photoperiod.
In May, when the birds are fat and nocturnally
active, pituitary
prolactin is released during the afternoon, whereas in
August, when the birds are lean and
nocturnally
inactive, the release of pituitary prolactin occurs between midnight and
sunrise (Meier, Burns and Dusseau, 1969).
In addition to the effects on fat stores
and locomotor activity, prolactin also affects the reproductive
systems in many
birds. In those birds in which prolactin
has an antigonadal
effect, it is generally
believed that prolactin inhibits the release
of follicle-stimulating
hormone
(Bates,
Riddle and Lahr, 19,37; Nalbandov, 1945).
On the other hand, prolact,in injections may
inhibit ovarian responses to exogenous follicle-stimulating
hormone and luteinizing
hormone when given early during a photoneriod of about 15 hr (Meier, 1969b). Injections given late in the day do not have
a significant inhibitory
effect, and injections at midday actually augment the gonndal responses to the gonadotropins
in
nhotorefractory
white-throated
sparrows.
Middav iniections of nrolactin also augthe gonadal resnonses to
ment greatly
exogenous FSH and LH in the whitecrowned sparrow on a long photoperiod
(Meier and Farner, 1964). Both early and

TEMPORAL

SYNERGISM

50.5

sparrows on eonlate injections of prolactin completely sup- sensitive white-throated

press the oviducal responses to FSH and tinuous light in mid winter (Meier, Martin
and MacGregor,
1971j. With respect to
LH in the white-throated
sparrow.
fat stores, the pattern
that developed
A role of adrenal steroids in the regulation of seasonal events has been investiwas essentially identical to that found in
the photorefractory
birds except that the
gated also in the white-throated
sparrow.
levels were higher in the photosensitive
Daily rhythms in levels of plasma corticontrols. That is, high levels of body fat
costerone were found in May and in August
were induced in birds receiving prolactin
in birds maintained in large outdoor hold12 hr after corticosterone and low levels
ing aviaries (Dusseau and Meier, 1971).
were induced by prolactin given 8 hr after
The daily rise in plasma corticosterone
occurs between
midnight
and sunrise corticosterone. In photosensitive as well as
(about 0300) in May, approximately
12 in photorefractory
white-throated
sparhr before the release of pituitary prolactin
rows, corticosterone
entrains a bimodal
(Meier; Burns and Dusseau, 1969). In rhythm of fattening response to prolact,iu.
The gonads of untreated
and control
August, the rise in corticosterone occurs
between sunset and midnight (about 2100)) white-throated
sparrows were enlarged in
approximately
6 hr preceding prolactin re- the photosensitive birds after about 2
lease. The birds in May were fat and not-. weeks in continuous light. Marked vari:+
turnally
active, and their gonads were tions in gonad weights were found in birds
recrudescing. The birds in August were which were treated with corticosterone aind
lean and inactive at night, and their gonads prolactin in 6 different daily patterns. Prola&n injected 12 hr after corticosterojle
were regressed.
With injections
of corticosterone
and augmented gonad weights whereas prolaciin
prolactin in photorefractory
white-throated
given 8 hr after corticosteronc suppressed
sparrows in August, we attempted to sim- gonad weights compared to control levels.
ulate the daily patterns of the endogenous
In general, the temporal patterns that, fahormones found in May and August (Meier
vored
fattening
also favored
gonadal
growth (Fig. 4).
and Martin, 1971). Prolactin causes rapid
gains in body fat in the photorefractory
In comparing the effe& cf exogenous
birds maintained on continuous light when corticoeterone and prolact,in when injected
it is injected 12 hr after injections of cortidaily at times that mimic the temporal
costerone. After only 5 days, the levels of relations of the hormone rhythms in Ylay
body fat reach values that are found in and August, the data support the hypothesis
feral birds during the migratory
periods that some of the seasonal differences in the
or in aviary enclosed birds in May. On the white-throated
sparrow are controlled by
other hand, prolactin injections given 8 hr a temporal synergism of these hormones
after eorticosterone are ineffective in stim(Fig. 4). While the daily rhythms of both
ulating fattening
and even cause further
hormones are entrained by the photoperiod,
reductions in fat stores in lean birds. A the phase angles of these rhythms with
lesser peak in fattening response to prorespect to the photoperiod
change from
lactin was found between O-4 hr after cor- May to August. The phase angles between
ticosterone.
Although
this
experiment
the two hormone rhythms also change from
lasted for only 5 days, there was evidence
May to -4ugust resulting in different metaof some gonadal
enlargement.
in the bolic and reproductive conditions. The segroup receiving prolactin 12 hr after cor- quentisi and cumulative net daily eRccts
ticosterone.
snmmate to produce the seasonal conditions
To pursue the possibility that the temwhich include characteristic daily patterns
poral synergism of corticosterone and proof loccmotor activitv, levels of body fat
lactin may also regulate the annual cycle stores, and reproductive
readiness. Thus,
of reproductive sensitivity to light, a sim- we believe that the temporal pattern of
ila,r experiment was performed with photocorticosterone and prolactin accounts for

506

ALBERT

Daily Rhythms
FIG. 4. Temporal
the white-throated

of Endogenous Hormones

H.

MElER

Conditions Simulated by Exogenous Hormones

synergism
of corticosterone
and prolactin
controlling
fat stores and gonadal
growth
in
sparrow.
Birds in May are fat and the gonads
are enlarging; birds in August
are lean and

the gonads are regressed.C = rise in plasma corticosterone,or corticosteroneinjection. P = releaseof pituitary prolactin, or prolactin injection. (Derived from Meier, Burns, and Dusseau, 1969; Dusseau and Meier,
1971; Meier and Martin, 1971; Meier, Martin and MacGregor, 1971.)
the conditions of metabolic and reproductive photosensitivity
and photorefractoriness in the white-throated
sparrow.
To document further the role of a temporal synergism of corticosterone and prola&in in controlling the sensitivity of the
reproductive
system to light, we tested
photorefractory
house sparrows, Passer
domes ticus, in continuous
light
(Meier,
Martin and MacGregor, 1971). The testes
weights of controls before and after the
experimental
period in September were
very small indicating that the birds were
in a photorefractory
condition. The testes
weights were enlarged in those birds which
received prolactin daily 4 or 8 hr after
corticosterone.
However, prolactin
injections given 0, 12, 16 or 20 hr after corticosterone did not stimulate or allow for
gonadal growth. The results were similar in
photorefractory
adults and in the young
which had no previous gonadal growth
(Fig. 5).
CONCLUDING

and developmental
events has received
little experimental
attention.
We believe
that the temporal synergism of adrenal
steroids and prolactin is an important organizer of the vertebrate system.
The organizational
aspects of the temporal synergism may be depicted from
several views. First, it seems to coordinate
I

REMARKS

It goes without saying that vertebrates

change with age and with the seasons. Some
of these changes (e.g., reproductive
and
migratory)
profoundly
affect the entire
organism. Although many of the changes
noted may be attributable
to specific hormones, the overall coordination
of the
many individual changes, and the arrangement of the orderly sequence of seasonal

0
Prolactin

lniections

s
(Hours

12

after

16
Cortlcosterone)

20

FIG. 5. Temporal
synergism
of corticosterone
and
prolactin
controlling
testicular
growth
in photorefractory
house sparrows
maintained
in continuous
light. The hormone
injections
were made daily for
14 days. Saline treated
controls
and untreated
controls
(dotted
line) averaged
2.2 and 2.0 mg, respectively.
(After
Meier,
Martin
and
MacGregor,
1971.)

TEIXPORAL

individual
tissues and activities so that
they summate to produce general organismal conditions. For example, the temporal pattern of hormones that stimulates
lipogenesis in the pigeon also stimulates
increases in intestinal
weight
(Meier,
Trobec, Joseph and John, 1971). Similarly,
the association of fattening and migration
in migrants appears to be set. by a particular hormonal pattern (Meier, 1969a).
Second, we believe that an orderly sequence
of developmental changes that occurs during the life of an animal may be regulated
in part by a changing temporal relation
between daily rhythms of prolactin and
adrenal steroids. For example, the temporal
pattern
of prolactin
and corticosterone
would control whether the spotted newt
a terrestrial
existence
or
maintained
whether
it, migrated
to water
(Meier,
Garcia and Joseph, 1971). Third, it coordinates
the organism
with
environmental changes (i.e., photoperiod)
so thst
appropriate
seasonal conditions may result. The seasonal changes are complex in
that the conditions are not direct reflections
of the photoperiod. That is, the interpretation of the photoperiod changes from one
season to another as a result. of the shifts
in phase angles of the hormone rhythms
with respect to the photoperiod.
Thus, a
given photoperiod
that produces a phase
angle equivalent to 12 hr between the daily
rise in plasma corticosterone and the daily
release of pituitary
prolactin in photosensitive birds in May produces a phase angle
equivalent to about 6 hr between the hormones in photorefractory
birds in August
(Meier, Burns and Dusseau, 1969; Dusseau and Meier, 1971).
It is apparent that many of the effects
of the temporal synergism of prolactin and
the adrenal steroids involve other hormones
as well. The temporal synergism of proiaetin and adrenal steroids could influence
both the production of, as well as the responses to, other hormones. These questions require further research.
ACKSOWLEDGMENTS
I am indebted
to my students
for their
ance at many
stages along the way in the
tion of data and in the preparation
of this

assistcollecstudy.

507

SYNEEGISM

Mr. Terry
Mr. Donn
paring
the

N. Trobec,
D. Martin
manuscript.

Mrs.
were

Maureen
of special

Trobec,
aid in

and
pre-

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DISCUSSION
GOURDJI:
Could
you give more
information
about. the stimulation
of the pigeon
cropsac
by adrenal
steroids?
MEIER:
There
is a marked
daily
variation
in tzhe cropsac
response
to prolactin
whether
it is given
systemically
or locally.
In addition,
corticosterone
can entrain
the local response
to prolaetin
whether
the steroid
is applied
systemically
or locally.
LICHT:
Despite
apparent
change
in pituitary
prolactin
at. certain
times,
prolactin
must
be in circulation
at all times.
How
do you relate
this to your
single injection
studies?
MEIER:
Studies
of endogenous
daily
rhythms
of prolactin
indicate
that there is a
daily
pulse
in the release
of pituitary
prolactin
in the white-throated
sparrow.
The
daily
injection
of prolactin,
we believe,
simulates
this effect.
There
is a precedence
in the pulsating
release
of LH to indicate
that the rapid rise in hormone
levels may
have important
functions
distinguishable
fro,m the steady
release.
ASSENMACHER:
Have
I understood
correctly
that
there
is a seasonal
fluctuation
of the location
of the circadian
peak in plasma
corticosterone
level?
MEIER:
There
is a shift in the time of rise of plasma
corticosterone
with
respect
to the photoperiod.
Although
the photoperiods
are of about
the same
length
in
May
and August,
the plasma
rise occurs
shortly
before
dawn
in May
and shortly
after dusk in August.
FARNER:
Inasmuch
as you have shown
that there are two patterns
of corticosterone
and prolactin
that
stimulate
fattening
in the white-throated
sparrow,
do you believe
that
the two patterns
account
for spring
and fall fattening?
MEIER:
Yes, we believe
that
the pattern
in which
prolactin
injections
follow
corticosterone
injections
by 12 hr stimulates
the spring
conditions
resulting
in
fattening
and gonadal
growth,
whereas
the pattern
in which
prolactin
follows
corticosterone
by 0 or 4 hr represents
the full conditions
resulting
in fattening
alone,
Mr.
Donn
Martin
has recently
completed
a study
in which
he has demonstrated
that
the 12-hr
pattern
of hormone
injections
stimulate
nocturnal
locomotor
restlessness
in the white-throated
sparrow
which
has a northerly
orientation
under
the
natural
early
spring
sky.
On the other
hand,
the 4-hr
pattern
induces
nocturnal
activity
which
has a southerly
orientation.

Co.,

Am-