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Independence of progesterone-induced facilitation and inhibition of lordosis behavior in ovariectomized guinea pigs
HORMONES
AND
BEHAVIOR,
5, 7-12
(1974)
Independence of Progesterone-Induced Facilitation and Inhibition of Lordosis Behavior in Ovariectomized Guinea Pigs L. P. MORINl Institute
of Animal
and H. H. FEDER Behavior,
Rutgers
University
In ovariectomized Hartley guinea pigs, 15 fig progesterone was shown to facilitate lordosis in 48% of animals when administered 36 hr after a 3.3 ng injection of estradiol benzoate. This dose of progesterone also inhibited lordosis behavior in 65% of animals administered an additional 0.6 mg progesterone at 60 hr. Significant inhibition of lordosis response to the 0.6 mg progesterone existed among animals in which lordosis was not facilitated by the initial 15 ng dose of progesterone. These results show that progesterone-induced inhibition can occur without prior facilitation of lordosis as tested by the manual stimulation technique.
There is considerable evidence that progesterone has both facilitatory and inhibitory effects on guinea pig sexual behavior (Dempsey, Hertz, and Young, 1936; Goy, Phoenix, and Young, 1966; Zucker, 1966; 1968; Zucker and Goy, 1967). About 8 hr after the facilitation of lordosis by preovulatory progesterone(Feder, Resko, and Goy, 1968), lordosis behavior terminates and is followed by a post-estrusrefractory period induced by progesterone(Goy et al., 1966; Zucker and Goy, 1967). During this time, lordosis is difficult to induce with exogenoushormones although progesteroneis nearly absent from peripheral plasma (Goy et aZ., 1966; Feder er al., 1968). With the increased plasmaprogesteronelevels during the luteal phaseof the estrouscycle, guinea pigs continue to be refractory to the actions of exogenous estrogen and progesterone (Feder et aZ., 1968; Goy et al., 1966). Zucker and Goy (1967) attempted without successto demonstratethat progesteronecould establishan inhibitory state, analogous to the post-estrus refractoriness seen in intact, cyclic animals,without first facilitating expressionof lordosis. Wade and Feder (1972) have recently demonstrated that the guinea pig midbrain concentrates progesterone to a greater extent than hypothalamus, hippocampus, or cortex. Progesterone implanted in the midbrain exerts
California
lkesent address: 94720.
Department
of Psychology,
7 Copyright All rights
0 1974 by Academic Press, Inc. of reproduction in any form reserved.
University
of California,
Berkeley,
8
MORINANDFEDER
inhibitory influences on lordosis responses(Morin and Feder, 1964a), whereas placement of this hormone in the hypothalamus facilitates lordosis (Morin and Feder, 1974b). These findings suggestedthat progesterone might be administered in a quantity which would be subthreshold for facilitation of lordosis but which would be concentrated sufficiently in the midbrain to provide an inhibitory action on lordosis even in the presence of adequate estrogen conditioning. The following experiment was designedto test this possibility, although limitations are necessarily placed on the collected data because lordosis was elicited by the manual stimulation technique rather than by vigorous males. METHODS Adult Hartley strain, albino female guinea pigs were obtained from Camm ResearchLaboratories (Wayne, NJ). Animals arrived at the laboratory weighing 350-450 gm and were ovariectomized under Innovar-vet (fentanyl and droperidol; Pittman-Moore, Washington Crossing,NJ, 0.05 ml per animal) and Equi-Thesin (Chloral hydrate and pentobarbital sodium; Jensen-Salsbery, St. Louis, MO, 0.6 ml per animal). Throughout the experiment, animalswere housed 6-8 per cage and were provided with Purina guinea pig chow and water ad lib. Fresh lettuce was provided three times weekly. Lights were on from 5 AM until 7 PM, and laboratory temperature was maintained at approximately 23” C. Ten to fourteen days after ovariectomy, all animals were given 3.33 pg estradiol benzoate (EB) followed 36-40 hr later by 0.6 mg progesterone (P). All hormones were administered subcutaneously in 0.1 ml sesameoil vehicle. Beginning 1 hr after P injection, animalswere tested for lordosis hourly for 10 hr. Only those animals which responded on two or more consecutive hours with lordoses which were held for more than one second duration were utilized during the subsequentexperiment. During this “screening” test and the experiment, testing was accomplishedby the manual stimulation method of Young, Dempsey, Hagquist, and Boling (1937). Twelve days after the screening test, all animals received 3.33 pg EB. Thirty-six hours later, the animals were randomly divided into groups which received the following treatments: Group A-O.6 mg P; Group B-oil vehicle; Group C-O.015 mg P. All animalswere then tested “blind” for lordosis for 10 hr (Test I). Sixty hours after estrogentreatment, all animalsreceived 0.6 mg P and were again tested hourly for 10 hr (Test II). Latency = the interval of time, in hours, between systemic P injection and first lordosis; maximum lordosis = the length, in seconds,of the longest lordosis displayed during the test period. Only responsesgreater than 1 set were consideredlordoses.Data concerning latency and maximum lordosis were used only if lordosis occurred on two or more consecutive hourly tests (Morin and Feder, 1964a,b).
PROGESTERONE
AND
LORDOSIS
9
BEHAVIOR
RESULTS During Test I, 0.6 mg P treated animals (Group A) displayed lordosis while the oil treated animals (Group B) did not (lo/ 12 vs I/ 12; p < 0.001; Fisher’s exact probability test). The choice of 0.015 mg P as a treatment for Group C is justified by the evidence that this amount of P is a threshold dose for facilitation of lordosis in estrogen primed animals(48% display heat; Fig. 1). Animals in Group C which responded to the low P dosedid not differ in lordosis characteristics as compared to animals treated with 0.6 mg P (Group A, Test I). Mean latencies (k SEM) for Groups A and C were, respectively, 4.79 + 0.02 and 5.00 _+0.39 hr; mean maximum lordoses were 9.36 + 1.75 and 11.70 f 1.77 set @ > 0.1 in each case; t-tests). During the last hour of testing 14/14 Group C and 7/l 0 Group A animalswhich had met the criteria for sexual behavior were still displaying lordosis. This indicates no difference in heat duration, at least through the 10 hr test period. The inhibitory effects of the various treatments were examined in Test II (Table 1). None of the Group A animals showed lordosis on Test II as compared with 75% of Group B (O/12 vs 9/l 2; p < 0.001; Fisher’s exact probability test). There is an overall inhibitory effect of 0.015 mg P on Group C responseduring Test II (1 O/29 Group C animals displayed lordosis vs 9/ 12 Group B animals; x’(l) = 4.09, p < 0.05). Of primary interest were those animals in Group C which did not display lordosis during Test I. After 1.00
2 UJ I
.75
z 30 p 5 8
.25
%
OIL
0.4 mg A mental
TEST
I
l ROe QOlSm#
B
C
Fig. 1. Proportion of ovariectomized guinea pigs in heat treatments 36 hr after estrogen priming (Test I).
following
various
experi-
10
MORIN
AND TABLE
Effect
+
1
of Oil, 0.6 mg or 0.015 mg Progesterone, 36 hr after EB on Sexual Behavior Response to 0.6 mg Progesterone 60 hr after EB
Group A B c (Cl
FEDER
C2)
Cl (no response on Test Cz (response on Test I)
I)
N
Test I treatment
12 12 29
0.6 mg P oil 0.015 mg P
0.00 0.85 0.35
15 14
0.015 0.015
0.20 0.50
mg P mg P
A vs B A vs C B vs C
p < 0.005 p = 0.018 p < 0.05
Cl ‘2, C2 C2
NS p < 0.01 p = 0.037 NS
vsA vsB vs A vsB
Test proportion
II responding
injection with 0.6 mg P for Test II, only 20% of these nonresponders (Subgroup Cr ) showed lordosis. This differs significantly from Group B, which did not receive P until Test II (3/15 vs 9/12; x2(1) = 8.15, p
DISCUSSION Fifteen micrograms of progesterone failed to facilitate lordosis in 15/29 animals, yet of these 15 animals (Group C r ; Table I), only 20% displayed lordosis in response to a subsequent injection of 0.6 mg progesterone. This clearly demonstrates that an inhibitory state can be induced with a dose of progesterone which is insufficient to facilitate lordosis. Such a finding is a reaffirmation of the independence of the inhibitory and facilitatory processes first demonstrated by Zucker and Goy (1967) through the use of metabolites of progesterone. Despite the present evidence that progesterone can inhibit without first causing facilitation, it has not been possible to clearly demonstrate a differential threshold of inhibitory and facilitatory mechanisms to proges-
PROGESTERONE
AND LORDOSIS BEHAVIOR
11
terone. Examination of Group C indicates a slight threshold difference, but subdivision of these animals into Test I nonrespondersor responders(Subgroups Ci and C,) indicates that inhibition by 0.015 mg progesterone occurred significantly only among animals which were not facilitated by that dose of progesterone. Therefore, among a subpopulation of guinea pigs in this experiment, progesterone may be facilitatory without inducing a post-estrus inhibition. Wade and Feder (1972a) have demonstrated selective uptake and retention of 3H-progesteronein guinea pig midbrain relative to other neural tissues. This evidence, in addition to the demonstration that progesterone implanted in guinea pig midbrain can inhibit lordosis behavior (Morin and Feder, 1972a), suggestedthat a threshold differential between the inhibitory and facilitatory actions of progesterone might exist. In view of the present results, however, it appears that the slight uptake differences between hypothalamus (a site of progesteronefacilitation) (Morin and Feder, 1974b) and midbrain are not sufficient to clearly distinguish a progesterone facilitation threshold from an inhibitory threshold. The present experiment also confirms severalpoints previously shown by other investigators. Large amounts of progesteronegiven 36 hr after estrogen priming will generally provide 100% inhibition of responseto a second large progesteronedose at 60 hr (present data and Zucker, 1966). This inhibition is not due to loss of estrogenic activity becauseestrogen priming can clearly remain in effect for at least 60 hr after injection (present data and Zucker, 1966). The threshold dose for progesterone facilitation of guinea pig sexual behavior has been demonstrated to be about 2Opg per animal (Wade and Feder, 1972). In the present experiment, 15 fig was sufficient to facilitate lordosis in about 50% of the animals. This very low progesteronedose, when facilitatory, appearsto act in an all-or-none manner, inducing sexual behavior characteristics not significantly different from animalswhich respond to much larger progesteronedoses(present data and Wade and Feder, 1972b). ACKNOWLEDGMENTS Supported by Research Scientist Development Award No. MH-29006 (to H. H. Feder) from the National Institute of Mental Health and by Research Grant No. HD04467 (to H. H. Feder) from the National Institute of Child Health and Human Development and a grant from the Alfred P. Sloan Foundation to Dr. D. S. Lehrman, Director, Institute of Animal Behavior. L. P. Morin was supported by Training Grant No. GM-1135 from the National Institute of Mental Health. Progynon-B was provided by the Schering Corporation. This is contribution No. 172 of the Institute of Animal Behavior. REFERENCES Dempsey, E. W., Hertz, R., and Young, W. C. (1936). The experimental induction oestrus (sexual receptivity) in the normal and ovariectomized guinea pig. Amer. Physiol. 116, 201-209.
of J.
12
MORIN AND FEDER
Feder, H. H., Resko, arterial plasma 505-513. Coy, R. W., Phoenix, luteum on the Comp.
J. A., and Cloy, R. W. (1968). Progesterone concentrations of guinea pigs during the oestrous cycle. J. Endocrinol.
in the 40,
C. H., and Young, W. C. (1966). Inhibitory action of the corpus hormonal induction of estrous behavior in the guinea pig. Gen.
Endocrinol.
6, 261-215.
Morin, L. P., and Feder, H. H. (1974a). Inhibition of lordosis behavior in ovariectomized guinea pigs by mesencephalic implants of progesterone. Bruin Res., in press. Morin, L. P., and Feder, H. H. (1974b). Hypothalamic progesterone implantation and facilitation of lordosis behavior in estrogen-primed ovariectomized guinea pigs. Brain Res., in press. Wade, G. N., and Feder, H. H. (1972a). (1,2-3H) Progesterone uptake by guinea pig brain and uterus: Differential localization, time-course of uptake and metabolism and the effects of age, sex, estrogen priming, and competing steroids. Brain Res 45, 525-543. Wade, G. N., and Feder, H. H. (1972b). Effects of several pregnane and pregnene steroids on estrous behavior in ovariectomized, estrogen-primed guinea pigs. Physiol. Behav. 9,113-175.
Young, W. C., Dempsey, E. W., Hagquist, C. W., and Boling, J. L. (1937). The determination of heat in the guinea pig. J. Lab. CZin. Med. 23, 300-302. Zucker, I. (1968). Biphasic effects of progesterone on sexual receptivity in the female guinea pig. J. Camp. Physiol. Psychol. 65, 412-418. Zucker, I., and Goy, R. W. (1967). Sexual receptivity in the guinea pig: Inhibitory and facilitatory actions of progesterone and related compounds. J. Comp. Physiol. Psychol.
64, 378-383.
AND
BEHAVIOR,
5, 7-12
(1974)
Independence of Progesterone-Induced Facilitation and Inhibition of Lordosis Behavior in Ovariectomized Guinea Pigs L. P. MORINl Institute
of Animal
and H. H. FEDER Behavior,
Rutgers
University
In ovariectomized Hartley guinea pigs, 15 fig progesterone was shown to facilitate lordosis in 48% of animals when administered 36 hr after a 3.3 ng injection of estradiol benzoate. This dose of progesterone also inhibited lordosis behavior in 65% of animals administered an additional 0.6 mg progesterone at 60 hr. Significant inhibition of lordosis response to the 0.6 mg progesterone existed among animals in which lordosis was not facilitated by the initial 15 ng dose of progesterone. These results show that progesterone-induced inhibition can occur without prior facilitation of lordosis as tested by the manual stimulation technique.
There is considerable evidence that progesterone has both facilitatory and inhibitory effects on guinea pig sexual behavior (Dempsey, Hertz, and Young, 1936; Goy, Phoenix, and Young, 1966; Zucker, 1966; 1968; Zucker and Goy, 1967). About 8 hr after the facilitation of lordosis by preovulatory progesterone(Feder, Resko, and Goy, 1968), lordosis behavior terminates and is followed by a post-estrusrefractory period induced by progesterone(Goy et al., 1966; Zucker and Goy, 1967). During this time, lordosis is difficult to induce with exogenoushormones although progesteroneis nearly absent from peripheral plasma (Goy et aZ., 1966; Feder er al., 1968). With the increased plasmaprogesteronelevels during the luteal phaseof the estrouscycle, guinea pigs continue to be refractory to the actions of exogenous estrogen and progesterone (Feder et aZ., 1968; Goy et al., 1966). Zucker and Goy (1967) attempted without successto demonstratethat progesteronecould establishan inhibitory state, analogous to the post-estrus refractoriness seen in intact, cyclic animals,without first facilitating expressionof lordosis. Wade and Feder (1972) have recently demonstrated that the guinea pig midbrain concentrates progesterone to a greater extent than hypothalamus, hippocampus, or cortex. Progesterone implanted in the midbrain exerts
California
lkesent address: 94720.
Department
of Psychology,
7 Copyright All rights
0 1974 by Academic Press, Inc. of reproduction in any form reserved.
University
of California,
Berkeley,
8
MORINANDFEDER
inhibitory influences on lordosis responses(Morin and Feder, 1964a), whereas placement of this hormone in the hypothalamus facilitates lordosis (Morin and Feder, 1974b). These findings suggestedthat progesterone might be administered in a quantity which would be subthreshold for facilitation of lordosis but which would be concentrated sufficiently in the midbrain to provide an inhibitory action on lordosis even in the presence of adequate estrogen conditioning. The following experiment was designedto test this possibility, although limitations are necessarily placed on the collected data because lordosis was elicited by the manual stimulation technique rather than by vigorous males. METHODS Adult Hartley strain, albino female guinea pigs were obtained from Camm ResearchLaboratories (Wayne, NJ). Animals arrived at the laboratory weighing 350-450 gm and were ovariectomized under Innovar-vet (fentanyl and droperidol; Pittman-Moore, Washington Crossing,NJ, 0.05 ml per animal) and Equi-Thesin (Chloral hydrate and pentobarbital sodium; Jensen-Salsbery, St. Louis, MO, 0.6 ml per animal). Throughout the experiment, animalswere housed 6-8 per cage and were provided with Purina guinea pig chow and water ad lib. Fresh lettuce was provided three times weekly. Lights were on from 5 AM until 7 PM, and laboratory temperature was maintained at approximately 23” C. Ten to fourteen days after ovariectomy, all animals were given 3.33 pg estradiol benzoate (EB) followed 36-40 hr later by 0.6 mg progesterone (P). All hormones were administered subcutaneously in 0.1 ml sesameoil vehicle. Beginning 1 hr after P injection, animalswere tested for lordosis hourly for 10 hr. Only those animals which responded on two or more consecutive hours with lordoses which were held for more than one second duration were utilized during the subsequentexperiment. During this “screening” test and the experiment, testing was accomplishedby the manual stimulation method of Young, Dempsey, Hagquist, and Boling (1937). Twelve days after the screening test, all animals received 3.33 pg EB. Thirty-six hours later, the animals were randomly divided into groups which received the following treatments: Group A-O.6 mg P; Group B-oil vehicle; Group C-O.015 mg P. All animalswere then tested “blind” for lordosis for 10 hr (Test I). Sixty hours after estrogentreatment, all animalsreceived 0.6 mg P and were again tested hourly for 10 hr (Test II). Latency = the interval of time, in hours, between systemic P injection and first lordosis; maximum lordosis = the length, in seconds,of the longest lordosis displayed during the test period. Only responsesgreater than 1 set were consideredlordoses.Data concerning latency and maximum lordosis were used only if lordosis occurred on two or more consecutive hourly tests (Morin and Feder, 1964a,b).
PROGESTERONE
AND
LORDOSIS
9
BEHAVIOR
RESULTS During Test I, 0.6 mg P treated animals (Group A) displayed lordosis while the oil treated animals (Group B) did not (lo/ 12 vs I/ 12; p < 0.001; Fisher’s exact probability test). The choice of 0.015 mg P as a treatment for Group C is justified by the evidence that this amount of P is a threshold dose for facilitation of lordosis in estrogen primed animals(48% display heat; Fig. 1). Animals in Group C which responded to the low P dosedid not differ in lordosis characteristics as compared to animals treated with 0.6 mg P (Group A, Test I). Mean latencies (k SEM) for Groups A and C were, respectively, 4.79 + 0.02 and 5.00 _+0.39 hr; mean maximum lordoses were 9.36 + 1.75 and 11.70 f 1.77 set @ > 0.1 in each case; t-tests). During the last hour of testing 14/14 Group C and 7/l 0 Group A animalswhich had met the criteria for sexual behavior were still displaying lordosis. This indicates no difference in heat duration, at least through the 10 hr test period. The inhibitory effects of the various treatments were examined in Test II (Table 1). None of the Group A animals showed lordosis on Test II as compared with 75% of Group B (O/12 vs 9/l 2; p < 0.001; Fisher’s exact probability test). There is an overall inhibitory effect of 0.015 mg P on Group C responseduring Test II (1 O/29 Group C animals displayed lordosis vs 9/ 12 Group B animals; x’(l) = 4.09, p < 0.05). Of primary interest were those animals in Group C which did not display lordosis during Test I. After 1.00
2 UJ I
.75
z 30 p 5 8
.25
%
OIL
0.4 mg A mental
TEST
I
l ROe QOlSm#
B
C
Fig. 1. Proportion of ovariectomized guinea pigs in heat treatments 36 hr after estrogen priming (Test I).
following
various
experi-
10
MORIN
AND TABLE
Effect
+
1
of Oil, 0.6 mg or 0.015 mg Progesterone, 36 hr after EB on Sexual Behavior Response to 0.6 mg Progesterone 60 hr after EB
Group A B c (Cl
FEDER
C2)
Cl (no response on Test Cz (response on Test I)
I)
N
Test I treatment
12 12 29
0.6 mg P oil 0.015 mg P
0.00 0.85 0.35
15 14
0.015 0.015
0.20 0.50
mg P mg P
A vs B A vs C B vs C
p < 0.005 p = 0.018 p < 0.05
Cl ‘2, C2 C2
NS p < 0.01 p = 0.037 NS
vsA vsB vs A vsB
Test proportion
II responding
injection with 0.6 mg P for Test II, only 20% of these nonresponders (Subgroup Cr ) showed lordosis. This differs significantly from Group B, which did not receive P until Test II (3/15 vs 9/12; x2(1) = 8.15, p
DISCUSSION Fifteen micrograms of progesterone failed to facilitate lordosis in 15/29 animals, yet of these 15 animals (Group C r ; Table I), only 20% displayed lordosis in response to a subsequent injection of 0.6 mg progesterone. This clearly demonstrates that an inhibitory state can be induced with a dose of progesterone which is insufficient to facilitate lordosis. Such a finding is a reaffirmation of the independence of the inhibitory and facilitatory processes first demonstrated by Zucker and Goy (1967) through the use of metabolites of progesterone. Despite the present evidence that progesterone can inhibit without first causing facilitation, it has not been possible to clearly demonstrate a differential threshold of inhibitory and facilitatory mechanisms to proges-
PROGESTERONE
AND LORDOSIS BEHAVIOR
11
terone. Examination of Group C indicates a slight threshold difference, but subdivision of these animals into Test I nonrespondersor responders(Subgroups Ci and C,) indicates that inhibition by 0.015 mg progesterone occurred significantly only among animals which were not facilitated by that dose of progesterone. Therefore, among a subpopulation of guinea pigs in this experiment, progesterone may be facilitatory without inducing a post-estrus inhibition. Wade and Feder (1972a) have demonstrated selective uptake and retention of 3H-progesteronein guinea pig midbrain relative to other neural tissues. This evidence, in addition to the demonstration that progesterone implanted in guinea pig midbrain can inhibit lordosis behavior (Morin and Feder, 1972a), suggestedthat a threshold differential between the inhibitory and facilitatory actions of progesterone might exist. In view of the present results, however, it appears that the slight uptake differences between hypothalamus (a site of progesteronefacilitation) (Morin and Feder, 1974b) and midbrain are not sufficient to clearly distinguish a progesterone facilitation threshold from an inhibitory threshold. The present experiment also confirms severalpoints previously shown by other investigators. Large amounts of progesteronegiven 36 hr after estrogen priming will generally provide 100% inhibition of responseto a second large progesteronedose at 60 hr (present data and Zucker, 1966). This inhibition is not due to loss of estrogenic activity becauseestrogen priming can clearly remain in effect for at least 60 hr after injection (present data and Zucker, 1966). The threshold dose for progesterone facilitation of guinea pig sexual behavior has been demonstrated to be about 2Opg per animal (Wade and Feder, 1972). In the present experiment, 15 fig was sufficient to facilitate lordosis in about 50% of the animals. This very low progesteronedose, when facilitatory, appearsto act in an all-or-none manner, inducing sexual behavior characteristics not significantly different from animalswhich respond to much larger progesteronedoses(present data and Wade and Feder, 1972b). ACKNOWLEDGMENTS Supported by Research Scientist Development Award No. MH-29006 (to H. H. Feder) from the National Institute of Mental Health and by Research Grant No. HD04467 (to H. H. Feder) from the National Institute of Child Health and Human Development and a grant from the Alfred P. Sloan Foundation to Dr. D. S. Lehrman, Director, Institute of Animal Behavior. L. P. Morin was supported by Training Grant No. GM-1135 from the National Institute of Mental Health. Progynon-B was provided by the Schering Corporation. This is contribution No. 172 of the Institute of Animal Behavior. REFERENCES Dempsey, E. W., Hertz, R., and Young, W. C. (1936). The experimental induction oestrus (sexual receptivity) in the normal and ovariectomized guinea pig. Amer. Physiol. 116, 201-209.
of J.
12
MORIN AND FEDER
Feder, H. H., Resko, arterial plasma 505-513. Coy, R. W., Phoenix, luteum on the Comp.
J. A., and Cloy, R. W. (1968). Progesterone concentrations of guinea pigs during the oestrous cycle. J. Endocrinol.
in the 40,
C. H., and Young, W. C. (1966). Inhibitory action of the corpus hormonal induction of estrous behavior in the guinea pig. Gen.
Endocrinol.
6, 261-215.
Morin, L. P., and Feder, H. H. (1974a). Inhibition of lordosis behavior in ovariectomized guinea pigs by mesencephalic implants of progesterone. Bruin Res., in press. Morin, L. P., and Feder, H. H. (1974b). Hypothalamic progesterone implantation and facilitation of lordosis behavior in estrogen-primed ovariectomized guinea pigs. Brain Res., in press. Wade, G. N., and Feder, H. H. (1972a). (1,2-3H) Progesterone uptake by guinea pig brain and uterus: Differential localization, time-course of uptake and metabolism and the effects of age, sex, estrogen priming, and competing steroids. Brain Res 45, 525-543. Wade, G. N., and Feder, H. H. (1972b). Effects of several pregnane and pregnene steroids on estrous behavior in ovariectomized, estrogen-primed guinea pigs. Physiol. Behav. 9,113-175.
Young, W. C., Dempsey, E. W., Hagquist, C. W., and Boling, J. L. (1937). The determination of heat in the guinea pig. J. Lab. CZin. Med. 23, 300-302. Zucker, I. (1968). Biphasic effects of progesterone on sexual receptivity in the female guinea pig. J. Camp. Physiol. Psychol. 65, 412-418. Zucker, I., and Goy, R. W. (1967). Sexual receptivity in the guinea pig: Inhibitory and facilitatory actions of progesterone and related compounds. J. Comp. Physiol. Psychol.
64, 378-383.