Effects of neonatal septal lesions on reproductive behavior of male and female rats

The purpose of this study was to examine the effects of neonatally placed septal lesions (SL) in male, female, and androgenized female rats on reproductive behavior. Animals were castrated as adults and tested for both feminine and masculine sexual behavior. After treatment with estradiol benzoate (EB) alone (2 μg daily for 3 days), only the females with SL which had not been given testosterone propionate (TP) neonatally showed a facilitation of lordosis behavior. Following EB (2 μg for 3 days) plus 0.5 mg progesterone (P), both the lesioned and the sham-operated female groups showed an increase in the display of lordosis in either hormonal condition. All animals were given a pretest for masculine sexual behavior and tested on Days 4, 7, 11, and 15 of daily TP treatment (150 μg/day). There was no effect of the neonatally placed SL on masculine sexual behavior in female rats or in female rats androgenized with 30 μg TP. However, lesioned females treated neonatally with 1 mg TP showed a marginal enhancement of masculine sexual behavior. Male rats given SL neonatally showed a marked enhancement of masculine sexual behavior compared to that of controls. These results suggest that, depending on the neonatal hormone environment, SL selectively increase behavioral sensitivity to hormones. Although neonatally lesioned females show behavioral responses similar to females given SL as adults, male rats given SL neonatally are unique in that they show enhanced masculine sexual behavior whereas males lesioned as adults do not.     

Facilitation of female sexual behavior in male rats by septal lesions: an interaction with estrogen.

Although destruction of the septal region markedly facilitates the lordosis behavior of female rats in response to estrogen priming, comparable lesions were found to be ineffective in facilitating the lordotic behavior of estrogen primed male rats. Neither the age at the time of septal destruction nor castration influenced the lordosis behavior of males. However, if prepubertal castrated males were given subcutaneous ovarian grafts or injected daily with 2 μgm estradiol benzoate (EB) during the 30 day period following septal destruction, a prolonged facilitation of the activational effects of EB on lordosis behavior was observed. Male rats subjected to septal destruction alone, chronic exposure to EB alone, exposure to ovarian grafts for 30 days prior to septal destruction, or chronic treatment with EB started 6 mo after septal lesioning, failed to show an increase in behavioral responsiveness to estrogen. Thus, in order for septal lesions to facilitate lordosis behavior of male rats, exposure to EB or ovarian tissue must occur within an apparent critical period following septal destruction. Adult male rats were found to be more responsive to this interaction of septal lesions and EB exposure than pubertal animals. It is suggested that the prolonged facilitation of lordosis behavior which follows septal destruction and estrogen exposure in the male rat may be due to hormonal modifications of the recovery process following brain damage.     

Inhibition of estrogen facilitation of sexual behavior by the intracerebral infusion of actinomycin-D

It has been shown previously that intracerebral actinomycin-D (Act-D) pellets inhibit estrogen facilitated female sexual behavior, but it was not possible to test the reversibility of this effect. In the present study an attempt was made to distinguish between the possible temporary interruption by Act-D of the biochemical action of estrogen which facilitates sexual receptivity and permanent toxic effects of the drug. Act-D in saline was infused into the third ventricle or the preoptic area (POA) to determine whether a reversible suppression of sexual behavior as measured by the lordosis quotient (LQ) could be produced. Ovariectomized rats were implanted with midline guide tubes entering the third ventricle (eight rats) or with bilateral tubes extending to the corpus callosum above the POA (67 rats). Each animal served as its own control since pretest and Act-D and recovery tests were performed 10–14 days apart in most subjects. For each behavioral test implanted subjects were primed with 3μg estradiol benzoate (EB) and 0.5 mg progesterone (P) 48 hr later. Behavioral tests, each involving 50 mounts, were performed 4–6 hr after P. Following the pretest the animals were retested under experimental conditions. Inner cannulae were inserted into the POA through the guide tubes and 0.11 μg Act-D infused 24 or 12 hr before, simultaneously with, or 6, 12, 18, or 26 hr after EB. A recovery test was performed 10–14 days later with no intracerebral infusion. The control procedure (infusion of of saline either simultaneously with or 12 hr after EB) did not alter the LQ. Act-D infusion produced a reversible suppression of lordosis which was dependent upon the time of administration of Act-D. Intraventricular infusion of Act-D 6 hr after EB reversibly inhibited lordosis behavior and no lesions were produced. Act-D infused into the POA simultaneously with EB or 6 hr later reversibly suppressed the LQ. In the 6 hr group, for example, the LQ fell from 78.3 to 35.7, but 10–14 days later reached 74.3. Although brain lesions of varying extent were produced by Act-D, the marked but reversible suppression of lordosis behavior is consistent with the view that Act-D inhibits estrogen facilitation of lordosis behavior by means of a biochemical rather than cytotoxic action.     

The reversible inhibition of steroid-induced sexual behavior by intracranial cycloheximide

Cycloheximide(Cyclo), an inhibitor of protein synthesis by a direct action on protein synthesis at the ribosomal level, was used to reversibly inhibit estrogen-induced sexual receptivity. Cyclo (100 μg per rat) was infused into the preoptic area(POA) of ovariectomized rats at varying times before, simultaneously with, and after 3 μg of subcutaneous estradiol benzoate (EB). All animals received 0.5 mg progesterone (P) 36 hr after EB, and were tested for sexual receptivity 4–6 hr after P. The females were placed with stud males and a lordosis quotient was computed for each female (lordosis quotient = number of lordosis responses/20 mounts by the male × 100). Females receiving Cyclo 6 hr before, simultaneously with, or 12 hr after EB showed significantly lower levels of sexual receptivity when compared to females receiving Cyclo 36 hr before and 18 and 24 hr after EB. When those animals that showed low levels of sexual behavior after Cyclo infusion were reprimed with EB and P 7 days later and presented with a male they showed high levels of sexual receptivity. Thus, the effect of Cyclo was reversible. Only Cyclo infusions into the POA (bilateral) and third ventricle were effective in suppressing sexual behavior. Caudate nucleus, lateral ventricle, and unilateral POA infusions were without effect.The data presented are in agreement with earlier work that utilized actinomycin D to inhibit steroid-induced sexual behavior. Cyclo was found to be less toxic than actinomycin D. All of the available evidence is consistent with the hypothesis that estrogen stimulates RNA and/or protein synthesis in its facilitation of sexual behavior in the female rat.     

Regulation of estrogen-stimulated lordosis behavior and hypothalamic progestin receptor induction by antiestrogens in female rats

Two estrogen antagonists, CI-628 (CI) and tamoxifen (TX), were used to examine the relationship between estrogen priming of lordosis behavior and progestin receptor induction in the hypothalamus-preoptic area (HPOA) of ovariectomized female rats. Lordosis behavior was assessed by measuring lordosis quotients (LQ) in response to injection of 2 micrograms of estradiol benzoate (EB) followed 48 hr later by 500 micrograms of progesterone (P). Behavior testing began 4 hr after P injection. The effects of antiestrogens were assessed by injecting CI and TX (1-2 mg) from 0 to 48 hr prior to EB. Levels of cytosol progestin receptor in the HPOA were determined by quantifying the specific binding of 0.5 nM [3H]R5020 to cytosols from animals receiving the same EB and antiestrogen treatments used in behavioral testing. TX given concurrently with or CI given 2 hr before EB abolished both lordosis behavior and induction of HPOA progestin receptors. In contrast, CI given 12 hr prior to EB abolished lordosis but permitted a 95% elevation in the concentration of progestin binding sites in the HPOA. TX or CI given 48 hr before EB resulted in moderate levels of lordosis (mean LQs from 56 to 69) and induction of HPOA progestin receptors from 85 to 130% above noninjected controls. However, CI given 24 hr prior to EB produced less than a 40% increase in brain R5020 binding even though lordosis behavior was equivalent to that seen in the 48-hr animals (mean LQ = 53). These data indicate that the effects of antiestrogens on female sexual behavior and on the synthesis of brain progestin receptors depend on which antiestrogen is used and the time interval between administration of estrogen and antiestrogen. They also demonstrate that under some conditions estrogen induction of cytosol progestin receptors in the HPOA can be dissociated from estrogen priming of lordosis behavior in rats.     

Hormonal Modulation of the Cutaneous Initiation of Lordosis in Infant and Adult Rats

The purpose of these experiments is to compare the regional specificity (Experiment 1) and the hormonal modulation (Experiment 2) of the cutaneous initiation of lordosis in 4- to 6-day-old male and female rats (infants) and in 60- to 90-day-old female rats (adults). In Experiment 1, subjects were primed with 100 μg estradiol benzoate (EB) and 0.5 mg progesterone (P) and were denervated on the Waist (dermatomes L1-L3), Midriff (dermatomes T10-L3), Flanks (dermatomes L4-L6), or Sides (dermatomes T10-L6). In infants, there were no significant differences between males and females. Denervation of the Waist. Midriff, or Sides but not of the Flanks significantly decreased the percentage of subjects displaying lordosis, lordosis quotient (LQ), and mean lordosis duration; no significant differences were obtained among Waist-, Midriff-, or Sides-denervated infants. In contrast, denervation of the Sides but not of the Waist significantly decreased LQ and mean lordosis intensity among adults. In Experiment 2, Waist-denervated infants and their surgical Controls were treated either with 100 μg EB and 0.5 mg P or with the oil vehicle; Waist-denervated adults and their surgical Controls received either 100 or 10 μg EB (no P). Regardless of hormone treatment, denervation of the Waist significantly decreased LQ and lordosis duration in infants and decreased LQ and lordosis intensity in adults. In infants, the only effect of priming with EB and P was to increase the percentage of pups showing lordosis and lordosis duration among the surgical Controls. In contrast, priming with 100 μg EB significantly increased the percentage of rats displaying lordosis, LQ, and lordosis intensity among Waist-denervated adults. These data suggest that cutaneous input from the Waist is important for eliciting lordosis in both infant and adult rats, and that the importance of this input is modulated by hormone priming in adult but not infant rats.     

Effects of progesterone implants in the habenula and midbrain on proceptive and receptive behavior in the female rat

Two brain areas behaviorally responsive to progesterone (P) were examined to determine their possible involvement in the control of rat preceptive behavior, i.e., solicitation behavior directed at the male. Progesterone implants were placed in the habenular nuclei and the interpeduncular nucleus-ventral tegmental area of the midbrain reticular formation (MRF). Different testing procedures and levels of priming with estradiol benzoate (EB) were used in order to distinguish the effects of P in either region on proceptive and receptive behavior during exposure to 10 mounts by stimulus males. To test for receptivity, sexually experienced 60-day-old ovariectomized (ovx) rats bearing stereotaxically placed guide cannulas extending to the habenula or MRF were given 10 μg EB subcutaneously. Forty-eight hours later, lordosis quotient (LQ) was determined. Immediately following this test, each animal was implanted with cholesterol (C) or P and was retested 2 hr later. Treatments for the proceptivity test were similar except that the animals received 2.5 μg EB/100 g body wt sc for 7 days before testing on the eighth day; LQ as well as hopping, darting, and ear wiggling were scored. In the receptivity test, P implantation in both the medial portions of the habenula and the MRF significantly increased lordosis above the levels found both in their preimplantation tests and following control implantation of C. Little proceptivity was observed. In the proceptivity test, P implants in both regions also significantly increased proceptive behavior above both types of control tests. All animals were highly receptive, and there was no difference in LQ among the groups. There was no increase of plasma P levels in similarly implanted animals during a 24-hr monitoring period, indicating that systemic leakage of the hormone was not responsible for the observed behavior. The data indicate that both the habenula and MRF are P-sensitive regions. Progesterone's action on the two areas facilitates expression of both proceptive and receptive components of female sexual behavior, indicating that the neural regulation of the two kinds of behavior is integrated at these levels.     

Hysterectomy-induced facilitation of lordosis behavior in the rat

The present study investigated the effect of hysterectomy on hormone-induced lordosis behavior. Lordosis quotients (LQ) were measured in hysterectomized-ovariectomized (HO) and ovariectomized-sham hysterectomized (OSH) rats after several treatments including either estradiol benzoate (EB) alone or EB plus progesterone (P) 44 hr later. Testing consisted of placing the females with sexually active males 48 hr after EB. In Experiment 1, HO animals treated with 5 μg/kg EB and 0.5 mg P had significantly higher LQs than OSH animals; groups treated with 10 μg/kg plus P were not different. Experiment 2 showed that a single injection of 50 μg/kg EB resulted in equally high levels of receptivity in both groups. The LQs of HO animals injected with 3 μg/kg for 4 days did not differ from those of OSH animals; however, the administration of 0.5 mg P 24 hr after the fourth EB injection resulted in significantly higher LQs in the HO group (Experiment 3). In Experiment 4, HO rats injected with 5 μg/kg EB and 0.1 mg P 44 hr later displayed higher levels of lordosis behavior than OSH animals. It was concluded that hysterectomy facilitated the lordosis behavior of ovariectomized rats injected with both EB and P and that the mechanism for this potentiation remains to be determined.     

Differential sensitivity of mounting and lordosis control systems to early androgen treatment in male and female hamsters.

The effects of early testosterone propionate (TP) treatment on the adult sexual behavior of hamsters were investigated in two experiments. In Expt. I, male and female pups were injected with oil vehicle or 1, 5, 10, 50, 100, or 250 μg of TP 24 hr after birth. In Expt. II, males and females received either oil or 10 μg of TP on the day of birth (Day 1), Day 3, Day 5, Day 7, or Day 9. At 70 days of age all animals were gonadectomized and 10 days later tested for lordosis behavior after estrogen and progesterone priming. One week after the test for female behavior all females began receiving 500 μg of TP each day and were tested for mounting and intromission behavior three times at 10 day intervals. Lordosis behavior was inhibited by as little as 5 μg of TP given 24 hr after birth. In males this dose produced the maximal effect, but in females increasing dosages resulted in a proportional decrease in lordosis duration. One μg of TP neonatally facilitated later mounting and intromission behavior in females and 250 μg of TP was no more effective than 1 μg. Lordosis duration was inhibited in females by 10 μg of TP on either Day 1 or 3, however, mounts and intromissions were facilitated by TP treatment on Day 1, 3, 5 or 7. These experiments demonstrate that the mechanisms mediating masculine behavior are more sensitive to neonatal TP treatment than are the mechanisms mediating lordosis behavior.     

Progesterone facilitation of lordosis in male and female Sprague-Dawley rats following priming with estradiol pulses

Adult male Sprague-Dawley rats rarely exhibit progesterone-facilitated lordosis following steroid treatments which are effective in females. In contrast, progesterone-facilitated lordosis has been observed following priming with estradiol pulses in another strain. The aim of this study was to compare progesterone-facilitated feminine sexual behavior in adult male and female Sprague-Dawley rats following priming with estradiol benzoate (EB) or estradiol pulses. Female sexual behavior was measured in adult, gonadectomized males and females treated as follows: Two pulses of estradiol followed by progesterone or oil the next day; EB (two doses) for 3 days, and progesterone or oil the next day. These protocols were repeated at 4- or 6-day intervals, respectively. Progesterone-facilitated lordosis was observed consistently in both sexes treated with estradiol pulses. By the fifth test, lordosis quotients did not differ between the sexes, but the lordosis ratings in progesterone-treated males remained lower than those observed in females. Proceptivity (hop-darting) was facilitated by progesterone in females, but was never observed in males. Lordosis was induced in both sexes by 15 micrograms EB, but was not reliably facilitated by progesterone. Treatment with the lower dose of EB (1.5 micrograms) induced high levels of receptivity in females (occasionally facilitated by progesterone), but not in males regardless of subsequent treatment (i.e, progesterone or oil). These data suggest that progesterone-facilitated lordosis can be induced in male Sprague-Dawley rats, if a regimen of estradiol pulses is used. Thus, the brain of the adult male is not inflexibly differentiated with regard to progesterone facilitation of feminine receptive behavior.     

A re-examination of the lordosis response in female rats given high doses of testosterone propionate or estradiol benzoate in the neonatal period

High lordosis quotients (LQ) were observed when female Wistar rats injected with 1.25 mgm of testosterone propionate (TP) on Day 4 of postnatal life were tested as intact adults. The high LQ was not due to testing during the lights-on period, the age at which the females were tested, the use of a strain that was insensitive to the masculinizing action of TP or estradiol benzoate (EB), the age at which the females were injected with TP or EB, or an abnormal response to estrogen. High LQ values were found in similar tests on adult female rats of two other strains injected with 1.25 mgm TP on Day 4 of life. A marked reduction of the facilitatory action of progesterone on receptivity in estrogen-primed animals was demonstrated in the females of all three strains treated with TP or EB during the neonatal period and for males after castration as adults.Analysis of the experimental records of the mating tests showed that females anovulatory following TP or EB administration during the neonatal period and tested either intact and under the influence of endogenous hormones or under the influence of exogenous estrogen showed a rapid and highly significant increase in receptivity during the course of prolonged (20 min) tests with two or three active stimulus males. This effect was very much reduced if the treated females were under the influence of exogenous estrogen plus progesterone. The effect was not seen in males castrated as adults and treated with estrogen, or in females not treated with steroids in the neonatal period and tested intact at proestrus alone or under the influence of exogenous steroids after ovariectomy. A significant increase in LQ during the test period was observed in females of the Wistar strain which were anovulatory as a result of exposure to constant light and were tested intact without any exogenous hormone being administered.It is suggested that although tests involving a limited number of mounts or attempts to mount at low rates over a short period of time may be adequate to determine the degree of receptivity of normal female rats they are not adequate to establish the capacity of female rats treated with steroid hormones during the neonatal period to display the lordosis response.     

Lordosis behavior in male rats after lesions in different regions of the corticomedial amygdaloid nucleus

The aim of the experiment was to study the effects of stereotaxic lesions of the anterior and the posterior regions of the corticomedial amygdaloid nucleus (CMN) on the display of lordosis behavior by the male rat. Animals were orchidectomized as adults and given estradiol benzoate and progesterone (P) sequentially. Sexual behavior testing was performed by 9 +/- 1 hr after P injection. Lesions placed into the posterior region of the CMN significantly decreased the proportion of animals showing lordosis behavior as compared to sham-operated and control animals. By contrast lesions in the anterior region of the CMN did not cause any changes in the proportion of animals displaying lordosis but markedly increased the lordosis quotient (LQ) of responding animals. The CMN was then concluded to exert a dual control in the display of lordosis behavior in the male rat with a posterior region regulating the willingness of animals to display lordosis behavior and rostral region subserving inhibitory mechanisms related to the sexual performance (LQ values).     

The effects of estrogen and progesterone on female rat proceptive behavior

The relative importance of estrogen (EB) and progesterone (P) in stimulating proceptivity in ovariectomized female rats was studied. Proceptive behavior was measured quantitatively, providing a clear measure of response to experimental manipulation. When rats were tested biweekly after daily treatment with 0.4 μg/100 g body wt EB for 4 days, they showed maximal lordosis but low levels of proceptive behavior by the second test. Additional EB (3.0 μg/100 g body wt daily) failed to stimulate additional proceptivity. A graded increase in proceptive behavior resulted from administration of increasing doses of P (50, 100, 500 μg and 1.0 mg) to animals receiving EB priming as described above. The level of “soliciting” was significantly higher than EB-only-treated rats when 500 μg or 1.0 mg P was given. Ovariectomized, adrenalectomized rats, primed with 2.5 μg/100 g body wt EB daily for 7 days and tested on Day 8, were significantly less proceptive than ovariectomized, sham-adrenalectomized rats with the same hormone treatment. Four hours after injection of 1.0 mg P, there was no difference in proceptive or receptive behavior between sham- and adrenalectomized rats. It was concluded that if an EB dose is sufficient to induce maximal receptivity, additional estrogen does not stimulate proceptivity; unlike previous studies, the present data are not consistent with a global effect of ovarian steroids on both components of female behavior. Progesterone is more effective than estrogen in stimulating proceptive behavior, although proceptivity is not absolutely dependent on progesterone for expression. Proceptivity in EB-only-treated rats appears to be facilitated by adrenal P.     

Musculinization and defeminization induced in female hamsters by neonatal treatment with estradiol, RU-2858, and nafoxidine

Newborn female hamsters were treated with 0.1 or 1.0 ng of estradiol benzoate (EB), with 1.0 ng–2.0 μg of the synthetic estrogen RU-2858, or with 0.1 or 0.5 μg of the antiestrogen nafoxidine. When adult the animals were treated with EB and progesterone and tested for the display of lordosis and with testosterone propionate and tested for the display of mounting behavior. The EB doses used failed to alter sexual differentiation. RU-2858 masculinized and defeminized in a dose-dependent manner being most effective when given neonatally as two divided doses. Nafoxidine inhibited lordosis without enhancing mounting behavior. The findings support the hypothesis that estrogens may be involved in the normal sexual differentiation process.     

Septal lesions: effects on lordosis behavior and pattern of gonadotropin release

Septal lesions increase behavioral responsiveness to estrogen of male, female, and androgen-sterilized female (ASF) rats as measured by lordosis behavior. Male and ASF animals normally show low levels of female sexual receptivity when compared to normal female rats. However, the level of female sexual behavior in male and ASF rats with septal lesions is comparable to that of highly receptive female rats. Progesterone facilitates the estrogen-induced female sexual behavior of female, but not male or ASF, animals. Andrenalectomy had no effect on the increased behavioral sensitivity to estrogen induced by septal lesions. Amygdala lesions, comparable in size to septal lesions, did not facilitate female sexual behavior. The male or female pattern of gonadotropin release is not affected by septal lesions, indicating a disassociation between the regulation of gonadotropin release and sexual behavior. Since septal lesions facilitate lordosis behavior in rats, the septal region appears to exert a tonic inhibition on female sexual behavior.     

A soy supplement and tamoxifen inhibit sexual behavior in female rats

In addition to displaying proceptive (hopping and darting) and receptive (lordosis) behaviors during a sexual encounter with a male, female rodents will regulate the timing of the encounter by engaging in a series of approaches and withdrawals from the male, a behavior termed paced mating behavior. Proceptive, receptive, and paced mating behaviors are all regulated by, and sensitive to, estrogen and progesterone, suggesting that compounds capable of disrupting these critical hormones may also perturb the display of female sexual behavior. The present experiments examined the impact of the selective estrogen receptor modulator (SERM) tamoxifen and a popular soy phytoestrogen dietary supplement on female sexual behavior in rats. Ovariectomized female rats were given either tamoxifen (TAMOX) by implant or the soy supplement through the diet then injected with estradiol benzoate (EB, 10 microg) or oil followed 48 h later with an injection of progesterone (P, 500 microg). Animals were then tested for sexual behavior 4 h after the P injection. Neither compound had any effect on sexual behavior when administered in conjunction with P alone; however, both significantly diminished receptive behavior, as measured by the lordosis quotient (LQ), in animals primed with both EB and P. Similarly, the hopping and darting rate was also significantly depressed in both the soy- and TAMOX-treated animals, compared to the EB- and P-treated controls, with the soy-treated animals showing significantly less proceptive behavior than the TAMOX-treated animals. Finally, soy but not TAMOX significantly attenuated paced mating behavior in animals compared to the EB- and P-treated controls. These results demonstrate that both the soy supplement and TAMOX act as estrogen antagonists on both proceptive and receptive behavior in female rats.     

Mounting behavior and lordosis behavior in castrated male rats treated with testosterone propionate, or with estradiol benzoate or dihydrotestosterone in combination with testosterone propinonate.

Treatment of prepuberally castrated male rats with testosterone propionate (TP, 50, 200, 500, or 1000 μg for 30 days) in adulthood stimulated the display of both mounting behavior and lordosis behavior. No correlation between mounting and lordosis behavior could be detected at any TP dose level. Treatment of prepuberally castrated male rats with either 1 μg estradiol benzoate (EB) or 500 μg dihydrotestosterone (DHT) for 60 days stimulated the display of mounting behavior in three of eight and four of eight rats, respectively. Treatment with 200 μg TP for the last 30 days of rats receiving either EB or DHT for 60 days resulted in an abrupt onset on mounting behavior as compared to rats treated with oil for 60 days. These results show additive effects of EB or DHT and TP upon mounting behavior by male rats and are interpreted as a support for the suggestion that testosterone to estrogen as well as testosterone to DHT conversion may be involved in the mechanism whereby testosterone activates the mounting behavior of castrated rats.     

Blockade of lordosis by androst-1,4,6-triene-3,17-dione (ATD) and tamoxifen in female hamsters primed with testosterone propionate

Normal female hamsters display lordosis after testosterone propionate (TP) plus progesterone (P) treatments. Such effect is probably mediated through aromatization of testosterone (T) into estradiol. If so, then an aromatase inhibitor (ATD) or an estrogen antagonist (tamoxifen, TAM) should be able to block the activational effect of T on lordosis. To test this hypothesis, 48 ovariectomized female hamsters were assigned into six groups which, according to treatments received, were ATD + TP, TAM + TP, OIL + TP, ATD + EB (estradiol benzoate), TAM + EB, and OIL + EB groups. The groups received assigned treatments for 2 days and were injected with P on the third day. Five minutes of behavior test was conducted 4 hr after P injection. The OIL + TP, OIL + EB, and ATD + EB groups all had averaged total lordosis duration (TLD) longer than 200 sec. The TLD of the TAM + EB group was only 117 sec. The ATD + TP and TAM + TP groups showed almost no lordosis. The results showed that the estrogen antagonist (TAM) impaired lordosis no matter whether the animals were primed with TP or EB, but the aromatase inhibitor (ATD) blocked lordosis only in TP primed females. It is concluded that the aromatization of T to estrogen is required for testosterone activation of lordosis in female hamsters.     

Postnatal thyroxine modifies effects of early androgen on lordosis

The sensitivity of female rats to the organizational effects of postnatal androgen was examined after néonatal manipulations known to affect the rate of brain development: thyroxine (T₄) administration and handling at birth. Testosterone propionate (TP) was injected subcutaneously in oil on postnatal day 6 to littermates that (i) had been undisturbed at birth; (ii) had received saline injections (S) and associated handling (H) on the day of birth (postnatal day 1) and the following day; and (iii) had received T₄ in saline (1 μg/g body wt) and H on postnatal days 1 and 2. Estrous cycles at 45 and 90 days of age, ovulation at Day 100 and sexual receptivity (lordosis score) at Days 115 and 125 were used to evaluate changes in TP effects. The majority of animals treated with 100 μg TP on postnatal day 6 exhibited persistent estrus (PE) at 45 and 90 days of age as expected. Neither T₄ nor S pretreatment on postnatal days 1 and 2 changed the incidence of PE. A reduction in ovarian weights and incidence of ovulation at 100 days of age supported cycle data in that only one out of 25 androgenized rats showed ovulation, compared with 16 of 22 controls. At approximately 115 days of age 2 μg of estradiol benzoate were administered for 3 days and 0.5 mg progesterone given on the 4th day 4 hr prior to placing females with sexually vigorous males. T₄-TP females exhibited higher (< .01) median lordosis scores than their S-TP littermates. The latter results were replicated in a second test conducted 10 days later (p = .002). In addition, the second test indicated that the S-TP group had lower (p = .005) lordosis scores than littermates given only TP neonatally. The results of these studies demonstrate that pretreatment with T₄ and handling, which are known, respectively, to hasten and retard the chronology of brain maturation, can exert differential effects on behavioral manifestations of postnatal TP without modifying androgen-induced sterility.     

The inhibition of steroid-induced sexual behavior by intrahypothalamic actinomycin-D

Lordosis behavior can be elicited in the ovariectomized rat after treatment with estradiol benzoate (EB) and progesterone (P) injections, but the EB must act for an extended period before P can facilitate this behavior. The possibility that this action of EB involves the stimulation of RNA or protein synthesis was tested by implanting actinomycin D (Act-D) directly into the preoptic area, one probable site of estrogen action. A total dose of 0.18 μg Act-D in bilateral cocoa butter pellets significantly inhibited lordosis behavior when implanted 12 hr after the injection of 3 μg. but not 15 μg EB. Implantation of this dose of Act-D subcutaneously, or intrahypothalamically 32 hr after EB injection, was without effect. Act-D placed in the ventromedial hypothalamus also suppressed lordosis, but implants in the caudate nucleus were without effect. At the time of the behavioral tests the animals were in excellent condition as determined by calculation of a health score, and no physical lesions were evident at the site of the implants. However, it was impossible to test the reversibility of this suppression of lordosis behavior since the animals became ill and many died within 1–2 weeks of implantation. The present results are consistent with, but not proof of, the concept that RNA synthesis may be essential for steroidinduced sexual behavior.