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A Review of Canine Pseudocyesis
C Gobello
1,2
, RL de la Sota
1
and RG Goya
2
1
Institute of Theriogenology,College of Veterinary Science (CC296) and
2
INIBIOLP-Histology B,Faculty of Medicine (CC455),National
University of La Plata,La Plata,Argentina
Contents
The purpose of this article is to review the most relevant
features of the physiology, clinical signs, diagnosis, treatment
and prevention of canine pseudocyesis (PSC). This is a
physiological syndrome, characterized by clinical signs such
as: nesting, weight gain, mammary enlargement, lactation
and maternal behaviour, which appears in non-pregnant
bitches at the end of metaoestrus. PSC is a frequent ®nding in
domestic dogs. Although it is generally admitted that
prolactin (PRL) plays a central role in the appearance of
PSC, its precise aetiophysiology is not completely understood
yet. A number of clinical studies suggest that at some point
of metaoestrus circulating PRL levels rise in overtly pseudo-
pregnant bitches. Individual dierences in sensitivity to PRL
as well as the existence of molecular variants of canine PRL
with dierent bioactivity versus immunoreactivity ratios may
help clarify the aetiopathology of PSC. Diagnosis of PSC is
based on the presence of typical clinical signs in metaoestrous
non-pregnant bitches. Considering that PSC is a self limiting
physiological state, mild cases usually need no treatment.
Discouraging maternal behaviour and sometimes ®tting
Elizabethan collars to prevent licking of the mammary
glands may suce in these cases. Sex steroids (oestrogens,
progestins and androgens) have been traditionally used to
treat PSC but the side-eects usually outweigh the bene®ts
of these medications. Inhibition of PRL release by ergot
derivatives [bromocriptine (10±100 lg/kg per day for
10±14 days], cabergoline (5 lg/kg per day during 5±10 days),
metergoline (0.2 mg/kg per day during 8±10 days) has proved
to be eective for the treatment of canine PSC. Although
some of these ergot derivatives present some untoward side-
eects, they are transient and can usually be managed.
Predisposed bitches not intended for breeding should be
spayed as ovariectomy is the only permanent preventive
measure.
Introduction
Pseudocyesis (PSC), pseudopregnancy, false pregnancy
or nervous lactation is a physiological syndrome char-
acterized by signs similar to those observed during the
post-partum period (Allen 1986; Jochle et al. 1987;
Arbeiter et al. 1988; Feldman and Nelson 1996). The
intensity of these signs is extremely variable among
bitches. Being an atavism, PSC could have had some
functional importance during evolution when non-bred
female wolves had to nurse other females' litters (Voith
1980; Jochle 1997). PSC is now a frequent ®nding in
domestic dogs and although its exact prevalence is not
known, it is estimated that it is as high as 50±75%
(Johnston 1980).
Although it is generally admitted that prolactin (PRL)
plays a central role in the genesis of PSC, its exact
aetiophysiology is not completely understood (Grunau
et al. 1996). A recent publication describes the concept
that PSC may be in¯uenced by nutritional practices
(Lawler et al. 1999). The purpose of this article is to
review the most relevant features of the physiology,
clinical signs, diagnosis, treatment and prevention of
PSC in the domestic bitch.
Endocrine features of the canine oestrous cycle
In comparison with other domestic and laboratory
species, the female dog has several reproductive features
that are unique. The bitch is monoestrus, with little
evidence of seasonality in most breeds. An obligatory
long anoestrus results in cycle intervals that can vary
from 5 to 12 months (Concannon 1986). The cycle is
characterized by the long duration of its phases (Jochle
1987). The periods of pro-oestrus and behavioural
oestrus are prolonged and variable, lasting between 3
and 20 days each. The pre-ovulatory luteinizing hor-
mone (LH) surge is considered as the central event of the
cycle (day 0, Concannon et al. 1977), with spontaneous
ovulation of primary oocytes from partially luteinized
follicles occurring around 48 h after the LH surge.
Oocytes undergo maturation during the next 2 or 3 days
in the oviduct (Concannon et al. 1977). The luteal phase
(LP) following oestrus is called metaoestrus, and hence
is the period associated with the function of the corpus
luteum (CL) and progesterone (P
4
) secretion. After day
30, P
4
secretion is dependent on pituitary secretion of
PRL and LH (Concannon et al. 1987; Arbeiter et al.
1988; Concannon 1993). Administration of dopaminer-
gic agonists, which lower the circulating PRL concen-
trations, has a complete luteolytic eect during the
second half of the LP (Concannon et al. 1987; Concan-
non 1993). The P
4
levels in unmated bitches are at a
maximum 2 or 3 weeks after ovulation and then decline
slowly to basal levels till the end of metaoestrus. The
long life of the CL in unmated dogs is related to the
absence of release of any luteolysin from the uterus
(Olson et al. 1984; Okkens et al. 1985). In the non-
pregnant cycle there usually is sucient stimulation of
mammary tissue by P
4
to make the metaoestrus a
physiologically distinct and recognizable period. Meta-
oestrus is considered to end when P
4
concentration
declines to basal levels (< 3 nmol/l). Obvious mam-
mary development may persist 1 or 2 months after P
4
reaches this basal level (Concannon 1986). There are a
few major endocrine dierences between pregnant and
non-pregnant cycles: in pregnant bitches, but not in
non-pregnant bitches, there is an elevation of relaxin
from day 25, and in PRL concentrations from day 30±35
until parturition (Concannon et al. 1996; Onclin and
Verstegen 1997).
Reprod Dom Anim 36, 283±288 (2001)
Ó2001 Blackwell Wissenschafts-Verlag, Berlin
ISSN 0936-6768
U. S. Copyright Clearance Centre Code Statement: 0936±6768/2001/3606±0283$15.00/0 www.blackwell.de/synergy
Clinical signs
Non-pregnant bitches in mid and late metaoestrus could
have signs of PSC but the intensity of these signs is quite
variable among them. Thus, some bitches have no signs
(covert PSC), whereas others show conspicuous signs
(overt PSC). This syndrome usually begins with
behavioural changes, such as restlessness, anorexia,
decreased activity, aggression, licking of the abdomen
and maternal behaviour (nesting, mothering inanimate
objects, adopting other bitches' puppies). Later, pseudo-
pregnant (PSPT) bitches show physical signs, such as
weight gain, mammary enlargement, milk secretion, and
sometimes abdominal contractions that mimic those of
parturition (Mialot et al. 1984; Feldman and Nelson
1996). Lactation is usually stimulated by self-nursing or
by suckling of unrelated neonates (Johnston 1980).
Vomiting, anorexia, diarrhoea, polyuria, polydipsia,
and polyphagia have also been reported (Johnston
1980). Bitches in which these signs are so exacerbated
as to become a clinical problem, are considered to
present clinical PSC and frequently need some kind of
treatment. Dierences in PRL bioactivity could explain,
at least to some degree, these wide variations in clinical
signs. In some women, no correlation between typical
signs of hyperprolactinaemia (HP) and serum PRL
concentrations has been detected (Jackson et al. 1985;
Larrea et al. 1985).
Complications of clinical PSC, such as mastitis and
mammary dermatitis, are not common and, unless these
complications appear, signs of PSC normally cease after
2±4 weeks (Johnston 1986). Susceptible bitches have a
high recurrence rate in successive oestrous cycles
(Johnston 1986; Feldman and Nelson 1996). Overt
PSC has also been observed after progestin treatment
and 3 or 4 days after ovariectomy during LP (Johnston
1980, 1986; Gobello et al. 2001). This is not surprising,
as these two situations of P
4
deprivation are quite
similar to luteolysis before parturition.
Aetiophysiology
It was initially postulated that PSC was caused either by
an overproduction of P
4
or abnormal persistence of CL
(Marshal and Halnan 1917). Later it was suggested that
clinical signs of PSC were related to the increased
concentrations of PRL caused by an abrupt decline of
P
4
levels in late LP (Smith and McDonald 1974; Gra
et al. 1977; Gerre et al. 1988; Concannon and Lein
1989). However, as this hormonal change occurs in both
pregnant and non-pregnant bitches it is dicult to
explain why overt PSP does not appear in all unmated
animals (De Coster et al. 1983; Fernandes et al. 1987).
Further evidence for a link between PRL and PSC was
provided by studies where the condition was successfully
treated by administration of PRL secretion inhibitors
(Mialot et al. 1981; Janssens 1986; Jochle et al. 1989;
Gobello et al. 2000b). In mammals, a preponderant role
of PRL is to stimulate the mammary gland during all
stages of development, from mammogenesis to the end
of lactation (Brugere 1998), although there are species
dierences in hormonal requirements for lactogenesis
(Forsyth 1986). In the bitch, PRL seems to be involved
in ensuring maternal behaviour, including the prepar-
ation for delivery and care of the litter thereafter. It is
not clear how PRL shares these eects with oxytocin
(McCarthy et al. 1992). Although PRL appears as the
most important endocrine factor controlling PSC, other
hormones might also play a role in keeping up the
process (Brugere 1998). In this regard it is of interest
that a positive correlation between PRL and oestrogens
has been found in certain bitches (Hadley 1975;
Olchewiski 1987).
Information is scarce regarding the 24 h secretory
patterns of PRL in the dog (Grunau 1994; Gobello et al.
2001a). Moreover, data on circulating PRL concentra-
tions in PSPT bitches are ambiguous because it is not
always taken into account whether PSC is clinically
overt, and because PRL assay methods dier among
studies. Thus, whereas in an early study, no signi®cant
dierences were found in PRL concentrations between
pregnant and covertly PSPT beagle bitches (Reimers
et al. 1978), two more recent studies in which dieren-
tiation between patients with overt and covert PSC was
attempted, did reveal dierences in PRL levels. These
latter reports involved clinical cases of dierent breeds.
In the ®rst of these studies, an overlap of PRL values
between covertly and overtly PSPT bitches was found
up to day 80 from the LH surge, as 55% of the PRL
levels of the PSPT animals were included within mean
SD of control covert bitches. In the same study PRL
levels were higher thereafter in overtly PSPT bitches
(Olchewiski 1987). In the second study, overtly PSPT
bitches had signi®cantly higher PRL levels than covertly
PSPT animals at day 60 of the oestrous cycle (Grunau
1994). A more recent study found higher PRL levels in
PSPT Afghan hound bitches when compared either with
Afghan hounds in an earlier stage of the LP or with non-
PSPT Beagles in the same stage (Okkens et al. 1997).
Although, most of the above results suggest that
increased PRL concentrations are responsible for overt
PSC, a recent study showed no signi®cant dierences in
mean serum PRL levels between PSPT and non-PSPT
bitches during 13 weeks in 28 Labrador Retrievers
(Lawler et al. 1999). A lack of signi®cant dierence in
PRL levels between surgery-induced PSPT and non-
PSPT animals has also been reported (Homann et al.
1992; Gobello et al. 2001), and an overlap of PRL serum
levels between PSPT and non-PSPT bitches post spaying
(Harvey et al. 1999). High PRL levels do not seem to be
necessary for the maintenance of PSP as suggested by a
report of low PRL levels in two spayed PSPT bitches
(Harvey et al. 1997). Therefore, a universal serum PRL
threshold for triggering PSC in the bitch is unlikely to
exist. The presence of molecular heterogeneity for PRL,
probably associated with dierent bioactivity, was
recently reported in 22 PSPT bitches, although no
signi®cant dierences in the proportion of each PRL
variant was found in this initial study (Gobello et al.
2000c).
No relationship was initially found between PSC
episodes and later reproductive diseases (Findler et al.
1966) or fertility problems (Johnston 1980). The number
of PRL receptors found in benign mammary tumours is
not higher than that of normal tissue and only 30% of
the malignant tumours have PRL receptors (Rutteman
284 C Gobello, RL de la Sota and RG Goya
and Misdorp 1989). Detailed studies on the endocrine
constellation conducive to the formation of mammary
tumours in the bitch have shown that growth hormone,
but not PRL, might be an augmenting factor (Graf and
Entrebay 1979). Nevertheless, PSC and PRL have been
recently implicated in the pathogenesis of mammary
tumours (Verstegen 1999).
Diagnosis
Diagnosis of PSC is based on the presence of the clinical
signs described above. As unscheduled matings may be
overlooked by owners, pregnancy should always be
considered, as both late pregnancy and PSC present
maternal behaviour. In case of doubt, ultrasound or
radiography should be used to arrive at a de®nitive
diagnosis. Other diseases of the LP, such as pyometra,
which can present anorexia, vomiting and depression
need to be ruled out by abdominal ultrasonography or
radiography, a complete blood cell count and additional
ancillary tests. It is also important to keep in mind that
PSC may coexist with other genital or extra-genital
clinical problems, sometimes making diagnosis more
dicult.
Other known causes of galactopoiesis associated with
HP, some of which may not be well characterized in the
dog, should be considered, especially if lactation lasts
longer than 3 or 4 weeks. Primary hypothyroidism, an
endocrine disease of high prevalence in the dog, is
associated with HP in some women; compensatory
elevation of thyrotropin-releasing hormone stimulates
both thyrotropin and PRL release (Larsen and Inbar
1992). Interestingly, a case of primary hypothyroidism
associated with HP in a cross-bred bitch has been
recently reported (Cortese et al. 1997). Other frequent
causes of HP in women, such as pituitary microadeno-
mas, hepatic or renal failure, sex steroids and psyco-
pharmaca administration remain to be assessed in the
bitch (Konig and Kopp 1986; Larsen and Inbar 1992).
Treatment
Considering that PSC is a self-limiting physiological
state, mild cases usually need no treatment. Hence,
discouraging maternal behaviour and sometimes ®tting
Elizabethan collars to prevent licking of the mammary
glands is recommended. Licking, milking, or hot or cold
packing the glands are all important stimuli for lactation
and therefore need to be avoided. Water removal for 5±7
nights forces ¯uid conservation and also helps termin-
ation of lactation; normal renal function should be
documented ®rst (Mialot and Bohnert 1980; Mialot
et al. 1984; Feldman and Nelson 1996). When beha-
vioural signs are important, light tranquilization with
non-phenotiazine drugs is useful. Phenotiazines are not
recommended as they stimulate PRL secretion (Voith
1983).
Sex steroids have been traditionally used to treat PSC
but the side-eects usually outweigh the bene®ts of these
medications. Although, sex steroids are necessary for
mammary development, high doses exert a negative
feedback on the hypothalamic±pituitary axis presuma-
bly inhibiting pituitary release of PRL (Johnston 1980;
Allen 1986). The most frequent sex steroids used
historically for the treatment of PSP are:
·Oestrogens such as diethylstilboestrol (DES), oestra-
diol benzoate or cypionate. They may cause signs of
pro-oestrus or oestrus, or induce uterine diseases,
such as pyometra, and bone marrow hypoplasia.
·Androgens such as testosterone have some virilizing
eect. The synthetic androgen mibolerone is some-
times indicated in bitches with behavioural signs of
PSC.
·Progestins such as megestrol acetate and medroxy-
progesterone acetate usually provoke a rebound in
lactation when treatments are discontinued as
removal causes the same hormonal status that initi-
ated the problem. Cystic endometrial hyperplasia±
pyometra complex, mammary gland nodules and
neoplasia, insulin resistance and acromegaly are some
of the most frequent complications of progestin
treatment (Feldman and Nelson 1996).
Inhibition of PRL secretion by ergot derivatives has
led to an important advance in the treatment of canine
PSC. Secretion of PRL by the pituitary is under tonic
inhibitory control of the hypothalamus, mediated
mainly by a direct inhibitory action of dopamine or
indirectly, by serotonin, a dopamine secretion suppres-
sant (Thorner et al. 1998). The most common com-
pounds used to inhibit PRL secretion are bromocriptine
and cabergoline which have a direct action on D
2
dopamine receptors of the anterior pituitary gland, and
metergoline which is a serotonin antagonist with a
dopaminergic eect at high doses (Hamon et al. 1981;
Janssen 1986; Jochle et al. 1989). Bromocriptine (Par-
lodel
Ò
, Sandoz, Bs. As. Argentina) has been used in
veterinary medicine since 1980. A large number of
therapeutic protocols have been proposed, using doses
ranging from 10 to 100 lg/kg per day for 10±14 days
(Mialot et al. 1981; Verstegen and De Coster 1985;
Janssen 1986). Side-eects of bromocriptine are frequent
and proportional to dose. They consist of vomiting,
anorexia, depression, behavioural changes (Peterson
and Drucker 1981). Vomiting can be managed by
administration of anti-emetic drugs. Care should be
taken not to use central dopamine blockers of the
synaptic transmission, such as metoclopramide, whose
action would oppose that of bromocriptine. To prevent
this side-eect it is advised that bromocriptine be
administered in either increasing doses or with the food
(Mialot et al. 1981, 1984). As bromocriptine comes in
2.5 mg tablets for use in humans in most countries,
fractioning is necessary to achieve the usual dose for
PSPY bitches (20 lg/kg per day) (Mialot and Bohnert
1980; Purswell 1998). Cabergoline (GalastopÒ; Vetem-
Centralvet s.p.a, Milan, Italy) has a higher level of
activity, superior speci®city and longer duration of
action than bromocriptine. It is indicated for PSPY
bitches at 5 lg/kg per day for 5±10 days. Cabergoline
scarcely crosses the blood±brain barrier and conse-
quently has much less central emetic side-eects (Jochle
et al. 1987; Arbeiter et al. 1988; Dumon et al. 1993;
Harvey et al. 1997). Metergoline (ContralacÒ; Vibrac
Laboratories, Carros, France) is used for 8±10 days at
0.2 mg/kg per day. Behavioural changes such as anxiety,
aggressiveness, hyperexcitation and whining are the
Canine Pseudocyesis 285
most frequent side-eects of metergoline, which are due
to its central antisertoninergic eect (Hamon et al. 1981;
Mialot and Dumon 1986; Arbeiter et al. 1995). There-
fore, metergoline should not be used in aggressive,
anxious bitches or those in which important behavioural
changes are already present due to PSC. On the other
hand, its emetic eect is very low but it has a weak
antiprolactinic eect as well as a short serum half life
(Fieni et al. 1999).
Predisposed bitches not intended for breeding should
be spayed, as ovariectomy is the only permanent
preventive measure (Johnston 1980, 1986). This should
preferably be done during anoestrus, never during
lactation as PSC may be perpetuated (Allen 1986; Mialot
et al. 1984). Spaying late metaoestrous bitches with a
history of overt PSC may provoke new episodes after
surgery (Gobello et al. 2001). Although obesity and
urinary incontinence could be long-term complications
of castration these can be managed with dietary control
and substitutive oestrogen therapy (Stubbs et al. 1995).
Discussion
Although PSC is the most frequent term used to
describe this syndrome in the English language, it is
not the most appropriate. Strictly, PSC is the LP of non-
fertile induced ovulatory cycles (Brugere 1998). More-
over, its signs are not similar to those of pregnancy but
to those of the post-partum period (Allen 1986).
Although it was once normal in wild dogs, PSC has
now become a clinical problem in most domestic bitches
bred as pets. PSC is relatively easy to diagnose
and treatment with dopaminergic agonists have
greatly helped in treating this syndrome (Arbeiter et al.
1988; Harvey et al. 1997, 1999; Gobello et al. 2001b).
Although some of them have some side-eects, they are
transient and can usually be managed.
Although the aetiophysiology of PSC is not fully
understood, a central etiologic role of PRL is widely
accepted. A number of hypotheses have been proposed
to explain why overt PSC appears only in some bitches.
The existence of predisposed breeds, although not
scienti®cally documented, is generally accepted. This
may be due to particular features of the oestrous cycle of
certain breeds. A short LP with an abrupt decline in P
4
levels, which would stimulate PRL release, has been
suggested to provoke PSC (Gerre et al. 1988; Concan-
non and Lein 1989). If this were so, all ovariectomized
dioestrous bitches should become PSPT after surgery.
However, only predisposed bitches become PSPT after
ovariectomy (Gobello et al. 2001). If levels of circulating
PRL do not necessarily determine the appearance of
PSC, the question of peripheral sensitivity to this
hormone must be taken into account. Thus, it can be
hypothesized that, for a given prolactinaemia, those
bitches with the highest sensitivity to PRL will be more
prone to developing overt PSC than animals with a
lower sensitivity to the hormone. This possibility has
already been considered by some workers (Mialot et al.
1981; Feldman and Nelson 1996). For this reason, a
universal serum PRL threshold for triggering PSC in the
bitch is unlikely to exist. Interestingly, research in
women has uncovered a surprising degree of molecular
heterogeneity for PRL, with dierent biopotencies
associated with varying molecular forms of the hormone
(Sinha 1995). In dogs, the presence of molecular
heterogeneity for PRL was recently reported in metaoe-
strous bitches (Gobello et al. 2000c). Therefore, dier-
ences in the bioactivity versus immunoreactivity ratios
of canine PRL in some bitches could account, at least in
part, for the lack of consistency between immunoassay-
able circulating levels of canine PRL and the presence of
a biological response namely, PSC. These unanswered
questions open exciting avenues of clinical and molecu-
lar research to unveil the molecular basis underlying the
phenomenon of PSC in the bitch.
Acknowledgements
The work reported here was supported in part by Grants from
the National University of La Plata (to RGG) and from the
Institute of Theriogenology (to CG and RLS).
References
Allen WE, 1986: Pseudopregnancy in the bitch. The current
view on aetiology and treatment. J Small Anim Pract 27,
419±424.
Arbeiter K, Brass W, Ballabio R, Jochle W, 1988: Treatment
of pseudopregancy in the bitch with cabergoline, an ergoline
derivate. J Small Anim Pract 2, 781±788.
Arbeiter K, Hofman E, Russe M, Kocks B, Ficus H, Jochle W,
1995: Metergoline zur behandlung von Pseudograviditat
und zur laktationsunterbrechung bei der Hundin.
Kleintierpraxis 4, 421±429.
Brugere H, 1998: The role of prolactin in the genital function
of the female dog. Rec Med Vet 174, 7±15.
Concannon PW, 1986: Canine physiology of reproduction. In:
Burke, T (ed.), Small Animal Reproduction and Infertility.
Lea and Febinger, Philadelphia, USA, pp 3±27.
Concannon PW, 1993: Biology of gonadotrophin secretion in
adult female dogs. J Reprod Fertil Suppl 47, 3±27.
Concannon PW, Gimpel T, Newton L, Castracane VD, 1996:
Postimplantation increase in plasma ®brinogen concentra-
tion with increase in relaxin concentration in pregnant dog.
Am J Vet Res 57, 1382±1385.
Concannon PW, Hansel W, McEntee K, 1977: Changes in
luteinizing hormone, progesterone and sexual behavior
associated with periovulatory luteinization in the bitch. Biol
Reprod 17, 604±619.
Concannon PW, Lein DH, 1989: Hormonal and clinical
correlates of ovarian cycles, ovulation, pseudopregnancy
and pregnancy in dogs. In: Kirk RW (ed.), Current
Veterinary Therapy X. WB Saunders, Philadelphia. USA,
pp 1269±1282.
Concannon PW, Westein R, Whaley S, Frank D, 1987:
Suppression of luteal function in dogs by luteinizing
hormone antiserum and bromocriptine. J Reprod Fertil
81, 175±180.
Cortese G, Oliva J, Verstegen J, Ciaramella P, Persechino A,
1997: Hyperprolactinemia and galatorrhea associated with
primary hypothyroidism in a bitch. J Small Anim Pract 38,
572±575.
De Coster R, Beckers JF, Beerens D, De Mey J, 1983: A
homologous radiommunoassay for canine prolactin: Plasma
levels during the reproductive cycle. Acta Endocrinol 109,
473±478.
Dumon C, Dumoulin PY, Collet JP, 1993: Traitement de la
lactation de pseudogestation chez la chien par la cabergo-
line. Pract Med Chir Anim Comp 28, 573±577.
286 C Gobello, RL de la Sota and RG Goya
Feldman EC, Nelson RW, 1996: Canine and Feline Endo-
crinology, Reproduction, 2nd edn. WB Saunders, Philadel-
phia, USA.
Fernandes PA, Bowen R, Kostas AC, Sawyer HR, Nett T,
1987: Luteal function in the bitch: changes during diestrus in
pituitary concentrations of and number of luteal receptors
for luteinizing hormones and prolactin. Biol Reprod 37,
804±811.
Fieni F, Vertegesten J, Heraud V, 1999: Physiologie de la
prolactine, pharmacologie des antiprolactiniques et appliac-
tions chez la chienne. Pract Med Chir Anim Comp 34,
187±199.
Findler IJ, Brodley S, Howson AE, Cohen D, 1966:
Relationship of anestrus irregularity, pseudopregnacy and
pregnancy to canine pyometra. J Am Vet Med Assoc 149,
1043±1104.
Forsyth IA, 1986: Variation among aspects in the endocrine
control of mammary growth and function: the roles of
prolactin, growth hormone and placental lactogen. J Dairy
Sci 69, 886±903.
Gerre S, Hoeveler B, Homan B, 1988: Canine pseudopre-
gnancy. Vet J Fur Den Veterinaer 5, 29±31.
Gobello C, de la Sota L, Castex G, Baschar H, Goya RG,
2001: Dioestrous ovariectomy: a model to study the role of
progesterone in the onset of canine pseudopregnancy.
J Reprod Fertil 57, 55±60.
Gobello C, Scaglia H, Colombani M, de la Sota L, Goya RG,
2001: Characterization of prolactin molecular variants in
pseudopregnant bitches. In: Forsberg, M., Greve, T.,
Gustafsson, H., Katila, T., Kinqahl, H., Ropstad, E. (eds),
Proc 14th Int Congr Anim Reprod, Stockholm, Sweden.
Elsevier, Stockholm, p. 117 (Abstr).
Gobello C, Bolognani F, de la Sota RL, Goya RG, 2001a:
Twenty four hour pro®les of serum prolactin and luteinizing
hormone in anestrous crossbred bitches. Reprod Dom Anim
36, 41±45.
Gobello C, de la Sota L, Goya R, 2001b: Study of the changes
of prolactin and progesterone during dopaminergic agonist
and placebo treatments in pseudopregnant bitches. Anim
Reprod Sci 66, 257±267.
Gra K, Entrebay K, 1979: Endocrinology of reproduction
in the female beagle dog and its signi®cance in mammary
gland tumorogenesis. Acta Endocrinol 90 (Suppl. 222),
1±33.
Gra K, Friendreich E, Matthews S, Hasan SH, 1977:
Homologous immunoassay for canine prolactin and its
application in several physiological states. J Endocrinol 75,
93±103.
Grunau B, 1994: Zur behandlung von Prolaktin bei Pseudogr-
aviditat der Hundin. Inaugural Dissertation. Tierarztliche
Hochschule, Hannover.
Grunau B, Nolte I, Hoppen HO, 1996: Investigation on the
treatment of pseudopregnancy in the bitch with the prolac-
tin inhibitors metergoline and bromocryptine. Tierarztl Prax
24, 149±155.
Hadley JC, 1975: Unconjugated oestrogen and progesterone
concentrations in the blood of bitches with false pregnancy
and pyometra. Vet Rec 96, 545±547.
Hamon M, Mallat M, Herbet A, Melson DL, Audinot M,
Glowinzki J, 1981: H3 Metergoline a new ligand of
serotonin receptor in the rat brain. J Neurochem 36,
613±626.
Harvey MA, Cauvin A, Dale M, Lindley S, Ballabio R, 1997:
Eect and mechanism of the antiprolactin drug cabergoline
on pseudopregnancy in the bitch. J Small Anim Pract 38,
336±339.
Harvey MA, Dale MJ, Lindley S, Waterson MM, 1999: A
study of the aetiology of pseudoprenancy in the bitch and
the eect of cabergoline therapy. Vet Rec 17, 433±436.
Homann B, Hoveler R, Hassan SH, Failing K, 1992: Ovarian
and pituitary function in dogs after hysterectomy. J Reprod
Fertil 96, 837±845.
Jackson RD, Worstman J, Malarkey WB, 1985: Characteri-
zation of large molecular weight prolactin in women with
idiopatic hyperprolactinemia and normal menses. J Clin
Endocrinol Metabol 61, 258±264.
Janssens LA, 1986: Treatment of pseudopregnancy with
bromocriptine, an ergot alcaloid. Vet Rec 119, 172±174.
Jochle W, 1987: The sexual cycle in the bitch: recent insights
and impact on therapy and reproduction. Tiera Prax 15,
295±300.
Jochle W, 1997: Prolactin in canine and feline reproduction.
Reprod Dom Anim 32, 183±193.
Jochle W, Arbeiter K, Post K, 1989: Eects on pseudopre-
gnancy, pregnancy and interoestrous intervals of pharma-
cological suppression of prolactin secretion in female dogs
and cats. J Reprod Fertil 39, 199±207.
Jochle W, Ballabio R, di Salle E, 1987: Inhibition of lactation
in the beagle bitch with the prolactin inhibitor cabergoline:
dose±response and aspects of long term safety. Therioge-
nology 27, 799±810.
Johnston SD, 1980: False pregnancy in the bitch. In: Morrow,
DA (ed.), Current Veterinary Theriogenology, 1st edn. WB
Saunders, Philadelphia. USA, pp. 623±624.
Johnston SD, 1986: Pseudopregnancy in the bitch. In: Mor-
row, DA (ed.), Current Veterinary Theriogenology, 2nd edn.
WB Saunders, Philadelphia, USA, pp. 490±491.
Konig MP, Kopp P, 1986: Hyperprolactinemia. Schweiz Med
Wochenschr 116, 265±270.
Larrea F, Villanueva C, Cravioto MC, Escorza A, del Real O,
1985: Further evidence that big-big prolactin is preferen-
tially secreted in women with hyperprolactinemia and
normal ovarian function. Fertil Steril 44, 25±30.
Larsen PR, Inbar SH, 1992: The Thyroid Gland. In: Wilson, J,
Foster; D (eds), Williams Textbook of Endocrinology, 8th
edn. WB Saunders, Philadelphia, USA, pp 357±487.
Lawler DF, Johnston SD, Ketlner DG, Ballman JM, Kealy
RD, Bunte T, Lust G, Mantz SL, Nie RC, 1999: In¯uence of
restricted food intake on estrous cycle and pseudopregnancy
in dogs. Am J Vet Res 60, 820±825.
Marshal FH, Halnan ET, 1917: On the post oestrus changes
occurring in the generative organs and mammary glands of
the non- pregnant dog. Proc Royal Soc London 89,
546±559.
McCarthy MM, Know LM, Pfa DW, 1992: Speculation
concerning the physiological signi®cance of central oxytocin
in maternal behavior. In: Pedersen, CA, Calldwell, JD (eds),
Oxytocin in Maternal Sexual and Socials Behaviors. Ann N
Y Acad Sci 652, 70±82.
Mialot JP, Bohnert M, 1980: Lactation de pseudogestation
chez la chienne. Le Point Veterinaire, Alfort, France, pp. 11,
33±35.
Mialot JP, Dumon CH, 1986: Utilisation de la metergoline
pour le tarissement de la lactation chez les carnivores
domestiques. Pract Med Chir Anim Comp 21, 177±181.
Mialot JP, Begon D, Guerin C, 1984: Pathologie de la
mamelle. In: Dumon, C., Fontbonne, A. (eds), Pathologie
de la reproduction chez les carnivores domestiques. Editions
de Point Veterinaire, Alfort, France, pp. 143±158.
Mialot JP, Lagneau F, Chaaux S, Badinand F, 1981:
Inhibition de la lactation de la pseudogestation chez la
chienne par la bromocryptine. Rec Med Vet 157, 351±365.
Okkens AC, Dieleman S, Bevers M, Willemse A, 1985:
Evidence of the non- involvement of the uterus in the
lifespan of the corpus luteum in the cyclic dog. Vet Quart 7,
169±172.
Okkens AC, Dieleman S, Kooistra HS, Bevers M,
1997: Plasma concentrations of prolactin in overtly
Canine Pseudocyesis 287
pseudopregnant Afghan hounds and the eect of metergo-
line. J Reprod Fertil Suppl 51, 295±301.
Olschewski C, 1987: Die lactatio falsa der Hunden: Klinische
und hormonanalytische Untersuchungen unter besonderer
Berucksichtigung einiger Therapieverfahren. Inaugural Dis-
sertation, Justus-Liebig University Giessen.
Olson PN, Bowen RA, Behrendt MD, 1984: Concentrations of
progesterone and luteinizing hormone in the serum of
diestrous bitches before and after hysterectomy. Am J Vet
Res 45, 149±153.
Onclin K, Verstegen JP, 1997: Secretion patterns of plasma
prolactin and progesterone in pregnant compared with non
pregnant diestrus beagle bitches. J Reprod Fertil Suppl 51,
203±208.
Peterson ME, Drucker WD, 1981: Advances in the diagnosis
and management of canine Cushing syndrom. In: (eds), Proc
31st Gaines Veterinary Symposium, Baton Rouge, p. 17.
Purswell BJ, 1998: Pharmaceuticals used in canine therioge-
nology. In: Society of Theriogenology (eds), Proc Annual
Meetings Soc Theriogenology, Baltimore, USA, pp. 92±97.
Reimers TJ, Phemister RD, Niswender GD, 1978: Radioim-
munological measurement of FSH and prolactin in the dog.
Biol Reprod 19, 673±679.
Rutteman GR, Misdorp W, 1989: Canine mammary tumor
disease: role of hormone in pathogenesis and treatment.
Tijdschr Diiergeneesk 114, 345±455.
Sinha YN, 1995: Structural variants of prolactin: occurrence
and physiological signi®cance. Endocrinol Rev 6, 354±369.
Smith MS, McDonald LE, 1974: Serum levels of luteinizing
hormone and progesterone during the estrous cycle, pseudo-
pregnancy and pregnancy in the dog. Endocrinology 94,
404±412.
Stubbs WP, Salmeri KR, Bloomeberg MS, 1995: Early
neutering of the dog and cat. In: Kirk RW (ed.), Current
Veterinary Therapy XII. WB Saunders, Philadelphia, USA,
pp 1037±1040.
Thorner MO, Vance ML, Laws RE, Horvath E, Kovath K,
1998: The anterior pituitary. In: Wilson, JD, Foster, DW,
Kronenberg, HM, Larsen, PR (eds), Williams Textbook of
Endocrinology, 9th edn. WB Saunders, Philadelphia, USA,
pp. 249±340.
Verstegen J, 1999: Interet et applications des antiprolactiques
en la cancerologie chez la chienne. In: World Small Animal
Veterinary Ass. (eds), Proc 24th World Small Animal
Veterinary Congress, WSAVA, Lyon, France. WSAVA,
Baltimore, USA
Verstegen J, De Coster R, 1985: Lactation nerveuse de la
chienne et bromocryptine. Ann Med Vet 125, 375±377.
Voith VL, 1980: Functional signi®cance of pseudocyesis. Mod
Vet Pract 61, 75±79.
Voith VL, 1983: Behavioral disorders. In: Ettinger, SJ (ed.)
Textbook of Veterinary Internal Medicine, 2nd edn. WB
Saunders, Philadelphia, USA, pp. 513±522.
Submitted: 15.01.2001
Authors' address: Cristina Gobello, Instituto de Teriogenologõ
Âa,
Facultad de Ciencias Veterinarias, UNLP, Cc 296, (1900) La Plata,
Argentina E-mail: cgobello@fcv.medvet.unlp.edu.ar
288 C Gobello, RL de la Sota and RG Goya
