Estradiol Benzoate Implants Research Articles

Evidence that desensitization to the negative estrogen feedback is a prepubertal and not a postpubertal event in female rats.

Female rats were ovariectomized at 31 days of age, on the day of proestrus, or on the day of the first vaginal estrus if corpora lutea were seen in the ovaries. Immediately after castration, estradiol-17 beta (E2) or oil was administered via s.c. silastics capsules, or a 1:240 mixture of estradiol benzoate (EB) and cholesterol or cholesterol alone was unilaterally implanted into the hypothalamic ventromedial-arcuate region. Forty-eight hours after surgery the rats were decapitated and the serum concentrations of LH and FSH estimated. In rats implanted s.c. with E2 in anestrus, proestrus or estrus, estrogen treatment reduced the circulating LH level to 9.4; 60.4 and 33.6% and that of FSH to 49.5; 120.3 and 63%, respectively, of the concentration recorded in the corresponding controls implanted with oil. Following the intrahypothalamic implantation of EB, the serum concentration of LH was lowered to 20.8; 67.4 and 68.1% and that of FSH to 48.8; 87.0 and 62.0% as compared to the cholesterol-implanted controls. The findings clearly suggest that a major part of the change in sensitivity to the negative feedback of estrogen occurs prior to the first preovulatory surge of gonadotrophins.

Hindbrain Administration of Estradiol Inhibits Feeding and Activates Estrogen Receptor-α-Expressing Cells in the Nucleus Tractus Solitarius of Ovariectomized Rats

17beta-estradiol (E2), acting via estrogen receptor (ER)-alpha, inhibits feeding in animals. One mechanism apparently involves an increase in the satiating potency of cholecystokinin (CCK) released from the small intestine by ingested food. For example, the satiating potency of intraduodenal lipid infusions is increased by E2 in ovariectomized rats; this increased satiation is dependent on CCK, and it is accompanied by increases in the numbers of ERalpha-positive cells that express c-Fos in a subregion of the caudal nucleus tractus solitarius (cNTS) that receives abdominal vagal afferent projections. To test whether direct administration of E2 to this area of the hindbrain is sufficient to inhibit food intake, we first implanted 0.2 microg estradiol benzoate (EB) in cholesterol or cholesterol alone either sc or onto the surface of the hindbrain over the cNTS. Food intake was significantly reduced after hindbrain EB implants but not after sc EB implants. Next we verified that equimolar hindbrain implants of E2 and EB had similar feeding-inhibitory effects and determined that only small amounts of E2 reached brain areas outside the dorsal caudal hindbrain after hindbrain implants of (3)H-labeled E2. Neither plasma estradiol concentration nor plasma inflammatory cytokine concentration was increased by either hindbrain or sc EB implants. Finally, hindbrain EB implants, but not sc implants, increased c-Fos in ERalpha-positive cells in the cNTS after ip injection of 4 microg/kg CCK-8. We conclude that E2, acting via ERalpha in cNTS neurons, including neurons stimulated by ip CCK, is sufficient to inhibit feeding.

Estrogen increases locomotor activity in mice through estrogen receptor alpha: specificity for the type of activity.

Estrogens are known to increase running wheel activity of rodents primarily by acting on the medial preoptic area (mPOA). The mechanisms of this estrogenic regulation of running wheel activity are not completely understood. In particular, little is known about the separate roles of two types of estrogen receptors, ERalpha and ERbeta, both of which are expressed in mPOA neurons. In the present study the effects of continuous estrogen treatment on running wheel activity were examined in male and female mice specifically lacking either the ERalpha (alphaERKO) or the ERbeta (betaERKO) gene. Mice were gonadectomized and 1 wk later implanted with either a low dose (16 ng/d) or a high dose (160 ng/d) of estradiol benzoate (EB) or with a placebo control pellet. Home cage running wheel activity was recorded for 9 d starting 10 d after EB implants. The same mice were also tested for open field activity before and after EB implants. In both female and male alphaERKO mice, running wheel activity was not different from that in corresponding wild-type (alphaWT) mice in placebo control groups. In both females and males it was increased by EB only in alphaWT, not alphaERKO, mice. In betaERKO mice, on the other hand, both doses of EB equally increased running wheel activity in both sexes just as they did in betaWT mice. Absolute numbers of daily revolutions of EB-treated groups, however, were significantly lower in betaERKO females compared with betaWT females. Before EB treatment, gonadectomized alphaERKO female were significantly less active than alphaWT mice in open field tests, whereas betaERKO females tended to be more active than betaWT mice. In male mice there were no effect of ERalpha or ERbeta gene knockout on open field activity. Unlike its effect on running wheel activity, EB treatment induced only a small increase in open field activity in female, but not male, mice. These findings indicate that 1) in both sexes estrogenic regulation of running wheel activity is primarily mediated through the ERalpha, not the ERbeta; and 2) hormone/genotype effects are specific to the type of locomotor activity (i.e. home cage running wheel activity and open field activity) measured.

The Effect of Esterification on the Release of Testosterone and Estradiol from Silicone Implants

Four experiments were conducted to determine the effect of esterification on the release of testosterone and estradiol from capsule-type silicone implants. In castrated male rats testosterone propionate and testosterone enanthate implants increased (P < .05) blood testosterone concentrations and seminal vesicle weights more than empty and testosterone implants. Testosterone propionate and testosterone enanthate implants released 4 times and 10 times, respectively, more equivalent testosterone per cm2 per day than testosterone implants. The increase in blood testosterone concentrations was proportional to the increase in implant release rate for testosterone propionate, but not for testosterone enanthate. Although estradiol- 17β implants increased (P < .05) uterine weights of ovariectomized rats, uterine weights in estradiol benzoate implanted ovariectomized rats were 1.3 times greater than in estradiol-17β implanted rats. Estradiol benzoate implants released less than 0.5 times the amount of equivalent estradiol per cm2 per day than estradiol- 17β implants.

The effects of intraventricular injection of β-endorphin on initial estrogen action to induce lordosis behavior

Ovariectomized female rats subcutaneously (SC) injected or intracerebrally implanted with estradiol benzoate (EB), and given progesterone SC were used as experimental animals to assess the effects of the β-endorphin (β-EP) neuronal system on lordosis behavior. In intraventricular (IV) injection of β-EP at the onset of sc EB priming, the lordosis behavior was significantly (p < 0.001) facilitated. In contrast, the lordosis behavior was significantly (p < 0.001) inhibited by IV injection of naloxone, an opioid receptor antagonist. β-EP facilitation of lordosis was observed exclusively within the initial stage of estrogen action. The behavior was significantly (p < 0.001) facilitated by IV injection of β-EP given with an intracerebral implantation of crystalline EB into the septal-preoptic regions. However, the lordosis behavior was significantly (p < 0.001) inhibited by β-EP when EB was implanted into the ventromedial hypothalamus. Animals receiving EB implants into the mesencephalic reticular formation were not affected by β-EP. The present study suggests that the β-EP neuronal system stimulates sexual receptivity through an action on the central nervous system in relation to the site of estrogen-initial activation to induce the lordosis reflex. The sites of β-EP action may be the estrogen receptive septal-preoptic and hypothalamic regions; the former for facilitatory effect and the latter for inhibitory effect.

Effect of progesterone on serotonin turnover in rats primed with estrogen implants into the ventromedial hypothalamus

The effect of progesterone (P) on serotonin (5-HT) turnover was studied in nine brain regions in ovariectomized rats primed with bilateral intracerebral implants of estradiol benzoate (1:250 cholesterol) directed towards the ventromedial hypothalamus (VMN). Two days after surgery, animals received P (0.5 mg SC), and were pretested for lordosis behavior. After a 44-h recovery period, rats with LQ ⩾60 were randomly divided into groups that received either a second behavior test or IP injections of saline or pargyline (4 h after P or V). P treatment decreased pargyline-induced accumulation of 5-HT in the VMN (pars lateralis), the lateral midbrain central grey (IMCG), and the periventricular region (PVE, anterior hypothalamic region). The 5-HIAA/5-HT ratios were significantly decreased in the VMN and PVE in P-treated animals. These results support the hypothesis that P-influenced decreases in serotonergic activity in the VMN contribute to the facilitation of female receptivity, and also suggest that steroid-mediated actions in the VMN may lead to changes in serotonergic activity in the IMCG and PVE.

Effects of steroid implants on the prepubertal increase in circulating gonadotropins and sexual receptivity in the female rabbit

The pubertal increase in gonadotropins in the female rabbit was inhibited 14–42-fold with Silastic implants of progesterone (P4) testosterone propionate (TP), estradiol benzoate (EB) or P4/EB placed subcutaneously on Day 24 of life. Rabbits with empty implants showed the normal prepubertal increase in circulating gonadotropins. By contrast, rabbits with implants of P4 only, had a 2-fold decrease in LH secretion when peak areas were compared. However, FSH secretion though slightly depressed was not significantly different from controls. The prepubertal increase in circulating gonadotropins was completely suppressed by implants of EB, TP and combined P4/EB. At 115-days-of-age, sexual receptivity and mating were absent in EB-treated animals and significantly suppressed in P4-treated ones when compared to controls, all of which mated. Mating was not completely inhibited in TP and combined P4/EB animals. Corpora lutea were found in all rabbits that mated. In the sexually non-receptive does, vaginal stimulation induced an LH surge in 2 of 15 animals. Ovarian weights and follicular development were significantly suppressed in rabbits with EB implants. Ovarian estradiol content was significantly increased in P4- and TP-treated rabbits. Maximum specific binding for [ 3H]naloxone was suppressed in the hypothalami of P4-treated rabbits. These results suggest that the prepubertal increase in circulating gonadotropins may have an essential role in the control of sexual maturation in the female rabbit.

Testosterone implanted in the preoptic area of male Japanese quail must be aromatized to activate copulation

Intracranial implantation of minute pellets of gonadal steroids was combined with aromatase inhibitor treatment to determine if aromatization within the preoptic area (POA) is necessary for androgens to activate sexual behavior in the Japanese quail ( Coturnix japonica). In this species, implantation of pellets of testosterone propionate (TP) or estradiol benzoate (EB) in the POA of castrated males restores male-typical copulatory behavior. In Experiment 1, adult male castrated quail were implanted intracranially with 200-μg pellets of equimolar mixtures of crystalline TP +cholesterol (CHOL), TP + 1,4,6-androstatriene-3,17-dione (ATD, an aromatase inhibitor), EB + ATD, or CHOL and behavior-tested with intact males and females. Copulation was stimulated by POA implants containing TP or EB (three of six CHOL + TP males and two of seven ATD + EB males copulated vs zero of four CHOL males), but copulation was not inhibited by combining ATD with TP (three of four ATD + TP males copulated). In Experiment 2, adult male castrated quail were injected systemically with ATD or oil for 6 days prior to and 14 days after intracranial implantation of 200-μg pellets containing the same amounts of TP or EB as in Experiment 1. The ATD injections completely blocked copulatory behavior in males with TP implants in the POA such that ATD TP and Oil/TP mount frequencies differed significantly, but failed to block copulation in males with EB implants in the POA (proportions of males copulating were ATD EB , 6 8 ; ATD TP , 0 6 ; Oil/TP, 4 7 ). The cloacal foam gland, an androgen-sensitive secondary sex character, was unaffected by the dose of ATD used. We conclude that activation of copulatory behavior by TP implants in the POA is not due to nonspecific effects of high local testosterone concentrations but rather to aromatization. These redults support the hypothesis that cells within the POA aromatize testosterone to estrogens, which directly stimulate the cellular processes leading to activation of male-typical copulatory behavior.

Activation of sexual behavior by implantation of testosterone propionate and estradiol benzoate into the preoptic area of the male Japanese quail ( Coturnix japonica)

Intracranial implantation of minute pellets of gonadal steroids was performed to determine neuroanatomical loci at which steroids activate sexual behavior in the Japanese quail ( Coturnix japonica). In this species, systemic treatment of castrated males with either testosterone propionate (TP) or estradiol benzoate (EB) restores male-typical copulatory behavior (head grabbing, mounting, and cloacal contact movements). In addition, EB activates female-typical receptive behavior (crouching). Adult male castrated quail were implanted intracranially with 300-μg pellets containing TP, EB, or cholesterol (CHOL) and behavior was tested with intact males and females. Either TP or EB pellets in the preoptic area (POA) activated male-typical copulatory behavior. Mounting was specifically activated without concomitant activation of other steroid-sensitive sexual and courtship behaviors. TP and EB implants in adjacent nuclei containing receptors for these steroids and CHOL implants in POA had no effect on male-typical copulatory behavior. Eighteen percent of all males tested for female-typical receptivity crouched, but no specific effect of EB was seen at any site. The similarity of the POA sites for activation of mounting by TP and EB is consistent with the hypothesis that cells within the POA aromatize testosterone to estrogens, which directly stimulate the cellular processes leading to behavioral activation.

Lesions in the preoptic area suppressed sexual receptivity in ovariectomized rats with estrogen implants in the ventromedial hypothalamus

The objective of the experiment was to determine if electrolytic ablation of a portion of the preoptic area (POA) influenced the activation of female lordosis behavior by implants of estradiol benzoate in the ventromedial hypothalamus (VMH) of ovariectomized (OVX) rats. Two weeks after ovariectomy, rats received either bilateral electrolytic lesions (2 mA for 10 sec in Experiment 1, or 1 mA for 5 sec in Experiment 2) in the POA, or sham lesions (all procedures except passage of current). On the same day (day 0 of the experiment) thirty-gauge stainless steel cannulae containing crystalline estradiol benzoate were stereotaxically placed bilaterally into the VMH of all the rats. Subsequently, females were tested for the lordosis response to stud males on days 2, 4, 6, 8, and 10 in Experiment 1 or on days 7, 14 and 15 in Experiment 2. All rats received 0.5 mg progesterone (SC) only before the last test. A female was considered sexually receptive if she exhibited a lordosis quotient (LQ) greater than or equal to 10 (LQ=No. lordosis responses/10 mounts by male × 100). The frequencies for sexual receptivity in females with POA lesions were significantly lower than those for control females without lesions in both experiments. Additionally the degree of receptivity (lordosis quotient) was significantly lower on each test day for rats with POA lesions than that for rats without POA lesions. The results imply that the maintenance of the integrity of the POA under this experimental condition was important for the expression of the facilitative influence of the VMH on lordotic responsiveness.

Dopaminergic involvement in the estrogen-induced suppression of frequency of pulsatile luteinizing hormone secretion in the ovariectomized rat

This experiment examined whether various catecholaminergic synthesis inhibitors and receptor blockers affect the inhibitory effect on the frequency of pulsatile luteinizing hormone (LH) secretion induced by local application of estradiol benzoate (EB) into the preoptic suprachiasmatic area (POSC) of ovariectomized rats. Ovariectomized rats were pretreated with either α-methyl- p-tyrosine (AMPT; tyrosine hydroxylase inhibitor), AMPT plus threo-dihydroxyphenylserine (DOPS; norepinephrine precursor), diethyldithiocarbamate (DDC; dopamine-β-hydroxylase inhibitor), pimozide (dopaminergic receptor blocker), phenoxybenzamine (α-adrenergic receptor blocker), propranolol (β-adrenergic receptor blocker), or their vehicles. EB implantation into the POSC reduced the frequency of existing pulsatile LH secretion in vehicle-treated rats. Pretreatment of the rat with AMPT, AMPT plus DOPS, or pimozide did not affect the basal pulsatile LH secretion but eliminated the suppressive effect of EB implantation on the LH pulse frequency. In rats pretreated with DDC or phenoxybenzamine, basal pulsatile LH secretion was significantly inhibited, and EB implantation did not lower serum LH further in these rats. Propranolol had no obvious effect on either basal pulsatile LH secretion or EB-induced suppression of LH pulse frequency. These findings suggest that, in addition to the α-adrenergic involvement in maintaining the basal pulsatile LH secretion, the intact dopaminergic system is required for the suppression of the frequency of LH pulses induced by estrogen.

Lack of gonadal control of the dorsal gland and sandbathing in male and female bannertail kangaroo rats ( Dipodomys spectabilis)

Previous studies have demonstrated gonadal control of mammalian scent glands; castration leads to reduced scent-marking rates and smaller gland sizes. I investigated whether gonadal hormones control the size of the dorsal gland (a specialized sebaceous gland) and sandbathing as a scent-marking behavior in adult male and female bannertail kangaroo rats ( Dipodomys spectabilis). Gland sizes of males and females were similar in all age classes, except adult males with larger body weights had proportionately larger glands than females. Male gland sizes declined 18% following castration but were not significantly smaller than those of intact males; females showed no change in dorsal gland size either as a result of ovariectomy or after estradiol benzoate implants. Sandbathing rates also did not decline as a result of gonadectomy. Rather, castrated males and overiectomized females sandbathed at higher frequencies than intact males and ovariectomized females with estradiol benzoate implants, respectively. Gonadal hormones apparently have little influence on the function of a specialized scent gland and may inhibit sandbathing as a scent-marking behavior in adult D. spectabilis.

Formation of behaviorally active estrogen in the dove brain: induction of preoptic aromatase by intracranial testosterone.

The preoptic area (POA) of the male ring dove is a target for specific behavioral effects of estrogen that are separable from those of androgen. Activity of the aromatase system in the POA, which converts testosterone to 17 beta-estradiol (E2), is increased by systemic androgen. Using crystalline steroid implants positioned stereotaxically in the brain, we examined whether aromatase induction is a result of direct steroid action on the POA, which can occur independently of the behavioral effects of androgen. Implants of testosterone propionate (TP) greater than 1.0 mm from POA nuclei were ineffective in increasing preoptic aromatase activity irrespective of whether the implants were unilateral, or bilateral with twice the potential output of testosterone. Within the 1.0-mm range, distance of implant from the POA nuclei was negatively correlated with induced aromatase activity in POA samples, indicating a direct effect of testosterone or its metabolites on enzyme activity. Induction of aromatase activity was higher in the right side of the POA than the left, suggesting asymmetry in inducible aromatase. Inactive 5 beta-reduced androstanes, 5 alpha-dihydrotestosterone and 17 beta-estradiol were formed from intracranial 3H-testosterone in POA. Since estradiol benzoate implants did not induce aromatase activity, this metabolite does not appear to act directly on the POA, although it is effective if administered systemically. Implants of TP in the region of the POA caused vocal behavior (perch calling) to be shown by some males. There was no correlation between the behavioral effectiveness of implants and induced POA aromatase activity. Since increase in E2 formation occurred in the absence of vocal behavior, activation of androgen-dependent behavior is not an absolute requirement for the induction effect. We conclude that testosterone can influence aromatase activity required for local production of E2 in the brain by direct action on POA cells.

Central vs. peripheral effects of estrogen on food intake and lipoprotein lipase activity in ovariectomized rats

The effects of implants of estradiol benzoate (EB) into either the ventromedial nucleus (VMH-EB) or the paraventricular nucleus (PVN-EB) of the hypothalamus were compared to the effects of peripheral EB (Per-EB) replacement in ovariectomized rats. After three days of hormone treatment, the Per-EB group and the PVN-EB group exhibited a decrease in food intake and body weight. Adipose tissue lipoprotein lipase activity was generally suppressed for the Per-EB, PVN-EB, and VMH-EB groups in the left and right parametrial and retroperitoneal fat pads. The finding that the VMH-EB and PVN-EB groups experienced similar peripheral stimulation but differed on the food intake and body weight measures would suggest that these measures are not entirely under peripheral control. The findings support the hypothesis that estrogen exerts its effects via multiple mechanisms, both central and peripheral. In addition, the PVN is shown to be an important site for further research on the modulation of feeding and metabolism by estrogen.

Angiotensin-estrogen central interaction: Localization and mechanism

Intracerebroventricular (ICVT) administration of estradiol benzoate (EB) to ovariectomized female rats decreased drinking and pressor responses to central injections of angiotensinn II (AII). Estrogen treatment does not have this effect in male rats. As EB given ICVT reaches many brain areas, the site of action of EB was localized using crystalline implants of EB in the medial preoptic area or the ventromedial nucleus of the hypothalamus. These areas were chosen as they have a high density of estrogen receptors. Only medial preoptic area application of estrogen decreased angiotensin II-induced drinking. Angiotensin receptor binding was examined in homogenates from different brain regions to determine if the mechanism through which estrogen decreases central responses to AII involves altered receptor function. Systemic EB did not affect AII receptor binding in several brain regions but binding was decreased in homogenates from the preoptic area and septum-thalamus blocks which encompassed structures (median preoptic nucleus, organum vasculosum, and subfornical organ) implicated in central actions of AII. The sex specificity of the effect of estrogen was dependent on sexual differentiation of the brain. Manipulation of the neonatal hormone environment, which alters this brain differentiation, also altered the characteristic responses of the two sexes to estrogen. Neonatal androgenization of females, which causes masculinization and defeminization, resulted in animals which as adults no longer responded to EB with decreased drinking. On the other hand, preventing the development of a male brain by neonatal castration produced animals which as adults tended to decrease their drinking following estrogen. In summary, this study found that EB acts in the preoptic area to depress AII-induced responses by a site specific modulation of central AII receptors. Alteration of early brain development changed the responses of the two sexes to estrogen, perhaps by altering sexual differentiation of the preoptic area.

Studies on the feedback regulation of pulsatile luteinizing hormone secretion: effect of ovarian steroid implantation into the forebrain and basal hypothalamus on pulsatile LH secretion in ovariectomized rats

Recent studies have demonstrated that ovarian steroids are involved in the regulation of pulsatile LH secretion. In order to identify the site of action of ovarian steroids in modulating pulsatile LH secretion, the effect of local administration of estradiol benzoate (EB) or progesterone (P) into various brain regions on the characteristic of LH pulses was investigated in ovariectomized rats. Female rats of the Wistar strain were ovariectomized about 3-4 weeks before the experiment. Blood samples were obtained at 6-min intervals for 4h without anesthesia through the indwelling atrial catheter. The steroid was implanted into the brain via the chronically-implanted cannula 1h after the initiation of the bleeding. Serum LH concentrations were determined by radioimmunoassay. The following results were obtained. Pulsatile LH secretion occurred at intervals of approximately 20-30 min and mean LH pulse amplitude was 4.85-5.27 ng/ml h in intact ovariectomized rats. Implantation of cholesterol, as a control, in various brain areas did not induce any changes in the pattern of pulsatile LH secretion. Implantation of EB into the preoptic suprachiasmatic area (POSC) rapidly decreased the mean serum concentration of LH within 1h as compared to the pre-implantation value. The LH pulse frequency, but not the amplitude, was also decreased rapidly and significantly within 1h after EB was implanted into the POSC. In rats with EB implanted into the diagonal band of Broca (DBB), LH pulse frequency began to decrease with 2h, followed by a decline in the mean LH concentration within 3h after the implantation. Implantation of EB into the medial part of the amygdala (m-AMYG) decreased the pulse frequency within 2h, and lowered the average LH level within 3h. The mean amplitude of LH pulses did not change after the implantation. Mean LH concentrations and LH pulse amplitudes began to decrease 1-2h after EB was implanted into the medial basal hypothalamus (MBH), whereas there was no change in the pulse frequency. Rats with the EB implant in the bed nucleus of the stria terminaris, the medial preoptic area, the medial septal nucleus or the anterior hypothalamic area did not show any changes in either the amplitude or the frequency of pulsatile LH secretion. Implantation of P into the DBB, POSC or MBH of ovariectomized rats did not induce any significant change in the pattern of pulsatile LH secretion. These results suggest that the sites of estradiol action in modulating characteristics of pulsatile Lh secretion are not widespread but rather concentrated within the specific brain regions.(ABSTRACT TRUNCATED AT 400 WORDS)

Differential Responsiveness of the Reproductive System of Blind or Melatonin‐Treated Male Hamsters to Injections of Gonadotrophin‐Releasing Hormone (GnRH) and/or Prolactin

The combination of pituitary grafts and daily injections of gonadotrophin-releasing hormone (GnRH) completely prevents gonadal atrophy in blind (BL) and melatonin (Mel)-treated male hamsters. In order to avoid potential problems associated with the use of pituitary grafts and further define the interactions between prolactin (PRL) and GnRH in preventing reproductive regression, we injected various doses of each hormone either alone or in combination into BL or Mel-treated male hamsters. In another experiment, BL hamsters received either weekly beeswax implants of estradiol benzoate (EB) (1 mg) alone or EB implants in combination with daily injections of GnRH (2 micrograms). In each experiment the hamsters were BL and/or treated with hormones for 10 wk. Either GnRH (8 micrograms) or PRL (5 micrograms) per d partially prevented gonadal atrophy in BL hamsters. However, increasing doses of GnRH plus PRL were more effective than either hormone alone in preventing gonadal atrophy. The combined effect of these hormones was greater than the algebraic sum of their individual effects. Injections of either GnRH or PRL alone resulted in a significant maintenance of gonadal and accessory organ size in Mel-treated animals. The combination of GnRH and PRL resulted in virtually complete maintenance of testicular weight while the accessory sex organs remained atrophic. The combined effect of these hormones was equivalent to the algebraic sum of their individual effects. The treatment of BL animals with EB implants with or without GnRH did not prevent reproductive regression in spite of elevated serum PRL levels. In conclusion, the effects of GnRH and PRL were synergistic in BL hamsters and additive in Mel-treated animals. The data suggest that there is a differential responsiveness of BL v. Mel-treated hamsters to the individual as well as the combined actions of GnRH and PRL.

Medial preoptic area, estrogen, and the peripubertal desensitization to the negative estrogen feedback in female rats.

Bilateral lesions placed in the medial preoptic area (MPOA) markedly diminished the luteinizing hormone-(LH-) and follicle-stimulating hormone- (FSH-) inhibiting effects of s.c. injected or intrahypothalamically implanted estradiol benzoate (EB) in ovariectomized immature rats. Desensitization to the negative estrogen feedback was also recorded in immature rats implanted into the MPOA with a mixture of 1 part EB and 240 or 360 parts cholesterol. Estrogen implants located in the hypothalamic ventromedial-arcuate region were ineffective in this regard. Whereas precocious puberty resulted from the implantation of EB into the MPOA, a delay of puberty onset was induced by medial preoptic implants of the antiestrogen clomiphene citrate which also enhanced the LH-suppressing effect of s.c. administered EB in prepubertal females. It is proposed that an increase of the estrogen concentration in the MPOA inactivates medial preoptic neurons that exert a restraining influence on tonic LH (and FSH) secretion by sensitizing the mediobasal hypothalamus to the negative feedback action of estrogen. This mechanism may be involved in the control of the onset of puberty in female rats.

Changes in the characteristics of pulsatile LH secretion after estradiol implantation into the preoptic area and the basal hypothalamus in ovariectomized rats.

Intracranial actions of estradiol benzoate (EB) in modulating the characteristics of pulsatile LH secretion were examined in ovariectomized rats. A minute amount of crystalline EB was implanted into the medial basal hypothalamus (MBH) or the preoptic suprachiasmatic area (POSC) and blood samples were collected at 6-min intervals for radioimmunoassay of serum LH concentrations. In rats with EB implanted in the MBH, the LH pulse amplitude decreased while the frequency did not change for 3 h after implantation. In rats bearing EB implants in the POSC, in contrast, the LH pulse frequency decreased without a significant variation in the pulse amplitude. Control animals with empty cannulae inserted into the MBH or POSC exhibited unchanged amplitude and frequency of LH secretory pulses. These results indicate that estrogen can regulate the amplitude and frequency of pulsatile LH secretion via mechanisms independent of each other. It appears that MBH and/or the pituitary is a site of the action of estrogen in decreasing LH pulse amplitude, while the POSC is a site of the steroid action in decreasing the pulse frequency.

Central plus peripheral stimulation by androgen is necessary for complete restoration of copulatory behavior in the male hamster.

Male golden hamsters were castrated and received a unilateral intrahypothalamic implant of either testosterone propionate (TP) or estradiol benzoate (EB). Half the animals from each group also received 5 alpha-dihydrotestosterone (DHT) via subcutaneous silastic capsule implants. The males were tested in a three-part design (intact, castrate, implant) to determine the effectiveness of intracerebral alone versus intracerebral plus systemic hormone regimens in restoring copulatory behavior following castration. All treatment regimens reinstated ectopic and normal mounting behavior to levels comparable to those seen in the intact animals. However, only those animals which received DHT systemically in addition to intracerebral implantation of TP or EB showed intromissions after castration. Both EB and TP groups with systemic DHT had intromission levels comparable to the controls by day 14 after implantation. The results point to a dual mechanism for the regulation of sexual behavior in the male hamster. A central hormone-sensitive mechanism is found in the anterior hypothalamic-preoptic region which is necessary for mounting behavior to be expressed. Androgen can affect stimulation at this level via conversion (aromatization) to estrogen. In addition, a peripheral hormone-sensitive mechanism which is necessary for intromission responses depends on the presence of nonaromatizable androgen for maintenance of its sensory feedback channels. The complete copulatory behavior pattern occurs only when both systems are hormone stimulated.