Physiological Pineal Effects on Female Reproductive Function of Laboratory Rats: Prenatal Development of Pups,Litter Size and Estrous Cycle in Middle Age

The present study investigates whether and how the pineal or its hormone melatonin influences female reproductive functions, namely the litter size, prenatal development of offsprings, and estrous cyclicity, especially its age‐related cessation in a non‐seasonal breeder, the laboratory rat. Wistar rats were maintained under a 24 h light‐dark (12L∶12D) cycle. Female rats were divided into 3 groups: non‐operated (NO), sham‐operated (SX), and pinealectomized (PX). Surgeries were performed in 35–40 day‐old females. Starting at an age between 70 days and 7 months, female rats of all 3 groups were repeatedly mated with intact males. PX mothers more frequently delivered pups with malformations (e.g., taillessness, hydronephrosis, 7 out of 1263 pups) than control rats (0/1323; p<0.007). In the first delivery at 3 months of age, but not at later ages, PX mothers delivered more pups of lower body weight than control animals (p<0.001). Examination of vaginal smears showed that almost all female rats of the NO, SX, and PX groups had 4‐day estrous cyclicity when they were young–between 60 days and 5 months of age. At an age of 17 to 18 months, most female rats of the NO and SX groups showed irregular, continuously diestrous or pseudopregnancy‐like patterns, and 4‐day estrous cyclicity was found in only 10% of the NO or SX animals. In contrast, about 50% of the PX rats showed 4‐day estrous cyclicity at this older age (p< 0.001). Melatonin, when added to drinking water (0.4 mg/L) for 16 days during the dark phase increased the frequency of diestrous phase, except in continuously diestrous rats and very few others. This melatonin effect was strong in PX rats but relatively weak in SX rats. In conclusion, the pineal hormone appears to influence various reproductive functions and developmental processes, especially pregnancy and the timing of reproductive aging in rats. The effects of pinealectomy are more prominent at an age of 60 to 80 days (i.e., shortly after puberty) and at the beginning of the cessation of cycles in middle‐aged females.     

Hypothalamic Neuroendocrine Functions in Rats with Dihydrotestosterone-Induced Polycystic Ovary Syndrome: Effects of Low-Frequency Electro-Acupuncture

Adult female rats continuously exposed to androgens from prepuberty have reproductive and metabolic features of polycystic ovary syndrome (PCOS). We investigated whether such exposure adversely affects estrous cyclicity and the expression and distribution of gonadotropin-releasing hormone (GnRH), GnRH receptors, and corticotrophin-releasing hormone (CRH) in the hypothalamus and whether the effects are mediated by the androgen receptor (AR). We also assessed the effect of low-frequency electro-acupuncture (EA) on those variables. At 21 days of age, rats were randomly divided into three groups (control, PCOS, and PCOS EA; n = 12/group) and implanted subcutaneously with 90-day continuous-release pellets containing vehicle or 5α-dihydrostestosterone (DHT). From age 70 days, PCOS EA rats received 2-Hz EA (evoking muscle twitches) five times/week for 4–5 weeks. Hypothalamic protein expression was measured by immunohistochemistry and western blot. DHT-treated rats were acyclic, but controls had regular estrous cycles. In PCOS rats, hypothalamic medial preoptic AR protein expression and the number of AR- and GnRH-immunoreactive cells were increased, but CRH was not affected; however, GnRH receptor expression was decreased in both the pituitary and hypothalamus. Low-frequency EA restored estrous cyclicity within 1 week and reduced the elevated hypothalamic GnRH and AR expression levels. EA did not affect GnRH receptor or CRH expression. Interestingly, nuclear AR co-localized with GnRH in the hypothalamus. Thus, rats with DHT-induced PCOS have disrupted estrous cyclicity and an increased number of hypothalamic cells expressing GnRH, most likely mediated by AR activation. Repeated low-frequency EA normalized estrous cyclicity and restored GnRH and AR protein expression. These results may help explain the beneficial neuroendocrine effects of low-frequency EA in women with PCOS.     

Role of nipple stimulation in the suppression of estrous cyclicity during extended lactation in the rat

The role of nipple stimulation in the suppression of the estrous cycle during extended lactation was studied in rats subjected to either total, partial, or sham excision of the nipples. Each female cohabited with 4 pups, 4-14 days old, over a period of 70 days postpartum, during which vaginal smears were recorded daily. Initially, regardless of the presence of nipples, all rats exhibited a postpartum diestrus that lasted for 12-20 days. Intact females (bearing 6 pairs of nipples) continued to exhibit successive prolonged diestrous phases over 70 days of lactation. A comparable result was obtained with females bearing only the anterior pair of nipples, which, in a separate experiment, was found to be the most frequently suckled pair. However, females devoid of nipples resumed regular (4-day) estrous cycles between Days 12 and 27 postpartum, in spite of their continuous contact with pups. Thus, when lactation is prolonged beyond the normal time of weaning (Day 21 postpartum), stimulation of the nipples by sucking becomes indispensable for the continued arrest of the estrous cycle. The possible mechanisms underlying this phenomenon are discussed.     

Inhibition of estrous cyclicity in golden hamsters by melatonin administration on the day of proestrus

Single injections of melatonin (25 micrograms) were administered to female hamsters, 15 minutes before lights-out (14L:10D), during either the early diestrous (day 1) or proestrous (day 4) phase of the estrous cycle. Hamsters which received melatonin only on the evening of proestrus became anovulatory by three weeks of treatment, while those that were injected with melatonin during diestrus, or administered oil on either day 1 or 4, continued to exhibit normal estrous cycles. These results indicate that quartan injections of melatonin can suppress reproductive function in female hamsters, and that the effectiveness of the injections may be dependent upon the stage of the estrous cycle at which they are administered.     

Reproductive toxicity assessment of lasofoxifene, a selective estrogen receptor modulator (SERM), in female rats

BACKGROUND: Lasofoxifene is a nonsteroidal selective estrogen receptor modulator (SERM). With high affinity to the alpha and beta human estrogen receptors and greater potency than other SERMs, lasofoxifene is potentially a superior treatment for postmenopausal osteoporosis. In light of the known effects of estrogen-modulating compounds on female reproductive indices, two studies were conducted to evaluate the effects of lasofoxifene on female rat cyclicity, reproduction, and parturition. METHODS: One study evaluated effects of lasofoxifene on estrous cyclicity, and the second study assessed effects on implantation and parturition. In the cyclicity study, lasofoxifene was administered to female rats at doses of 0.1, 0.3, and 1.0 mg/kg/day for 14 consecutive days. After treatment, there was a 3-week reversibility phase followed by a mating phase. In the implantation study, lasofoxifene was administered to pregnant female rats at doses of 0.01, 0.03, and 0.1 mg/kg/day for 7 consecutive days (gestation day [GD] 0-6). Some animals were euthanized on GD 21, and the remainder of the group was allowed to deliver the F1 generation. Several developmental indices were evaluated in the F1 pups through post-natal day (PND) 21. RESULTS: In the cyclicity study, all lasofoxifene-treated females were anestrous by Study Day 7 (1.0 mg/kg) or 9 (0.3 and 0.1 mg/kg). The reversibility phase resulted in restoration of normal estrous cycles by the end of 1 (0.1 mg/kg) or 2 weeks (0.3 and 1.0 mg/kg). During the mating phase, no adverse effects occurred in pregnancy success or reproductive parameters. In the implantation study, all doses of lasofoxifene increased pre- and post-implantation losses, increased gestation length, and reduced litter size. None of the developmental parameters measured on the F1 generation was adversely affected. CONCLUSION: Lasofoxifene reversibly altered the estrous cycle and inhibited implantation, consistent with what would be expected from a member of the SERM class.     

Photoperiodic modulation of sexual and aggressive behavior in female golden hamsters (Mesocricetus auratus): role of the pineal gland

Pinealectomized female hamsters (Mesocricetus auratus) housed in a short-day photoperiod were ovariectomized and tested for hormone-induced sexual receptivity in order to investigate the role of the pineal gland in the control of behavioral sensitivity to exogenous ovarian steroid hormones (Experiment 1). Behavioral sensitivity to hormones was further investigated in females maintained in a long-day photoperiod and rendered acyclic by daily administration of exogenous melatonin (Experiment 2). Female aggressive behavior was also monitored in all tests. Pinealectomy did not affect the reduced behavioral sensitivity to exogenous estrogen (E) induced by short days. These animals were also partially refractory to the effects of E when combined with low doses of progesterone. In addition, although melatonin administration mimicked the effects of short days on estrous cyclicity, the expression of hormone-dependent behaviors in these animals resembled the pattern displayed by control animals kept in long days. Thus, these findings suggest that the pineal gland plays a negligible role in the photoperiodic modulation of hormone-dependent sociosexual behaviors in female hamsters.     

Relation of parity and estrous cyclicity to the biology of pregnancy in aging female rats

In the female rat, the incidence of regular estrous cyclicity and fertility decreases progressively during aging, and the causes for these are unknown. To reveal the biology of pregnancy in aging rats, we performed a longitudinal study in a colony of multiparous rats bred every 2 mo. Beginning at 4 mo and continuing to 12 mo of age in these same individual females, we determined the chronological changes in estrous cyclicity, examined the relationship between the estrous cycle pattern and fertility, and recorded the numbers of live and dead pups delivered at term. In separate groups of 4- to 12-mo-old multiparous rats, we counted the number of ova present in the oviducts (ovulation rate) one day after mating and the number of grossly normal blastocysts found in the uteri on Day 5 of pregnancy. Similar studies were also performed in primiparous rats of 8, 10, and 12 mo of age. The cessation of regular cyclicity during aging occurred significantly (p less than 0.01) earlier in virgin than multiparous rats. Fertility followed a similar but more dramatic pattern of decline than did the incidence of regular cyclicity in both the multiparous and virgin females. Few irregularly cyclic and persistent-estrous females had fertile gestations after mating, and increasing proportions of regularly cyclic females also failed to reproduce successfully at middle age (8-12 mo). Thus, regular ovulatory cycles were essential but not sufficient for fertile gestations in aging rats. Beginning at 6 mo of age, the litter sizes of multiparous rats decreased progressively, and these decreases were associated with a similar decline in the number of live but not dead pups delivered. Also, the percentage of dead pups/total number of pups delivered increased steadily during aging in multiparous (from 14% to 69%) but not primiparous females. The litter sizes of 8- to 10-mo-old primiparous females were not different from those of multiparous rats. However, the litter sizes of irregularly cyclic rats were consistently smaller than those of regularly cyclic females. Thus, parity had little effect on fecundity in aging females, whereas the cessation of regular ovulatory cycles during aging greatly decreased both the incidence of fertility and the litter size.(ABSTRACT TRUNCATED AT 400 WORDS)     

Melatonin in rat milk and the likelihood of its role in postnatal maternal entrainment of rhythms

The rhythm of melatonin in rat milk and the capacity of pups to synthesize and metabolize melatonin were studied. Melatonin was undetectable in milk in the light (< 21 pM), but increased rapidly 2-4 h after dark to peak at 357 +/- 66 pM at mid-dark. Oral or subcutaneous administration of melatonin to 5- and 10-day-old pups resulted in peak plasma melatonin levels 30 min after administration and rapid metabolism. Increases in pineal and plasma melatonin levels at night were detected at 5 and 6 days of age, respectively. Isoproterenol administration (2 microg/g body wt) at mid-light to day 10 pups increased plasma melatonin from 312 +/- 40 pM to 1,298 +/- 160 pM, whereas propranolol (2 microg/g body wt) suppressed nocturnal melatonin secretion from 1,270 +/- 128 pM to 395 +/- 66 pM. The rise of pineal and plasma melatonin in day 10 pups occurred 1 and 2 h after dark onset, respectively, preceding the onset in dams by 3 and 4 h, respectively. Propranolol administration to 2- and 5-day lactating dams inhibited plasma and milk melatonin at night but had no effect on their suckling pups. Transfer of melatonin via the milk is unlikely to provide an entraining signal for rat pups.     

Endocrine disrupting effect of di-(2-ethylhexyl)phthalate on female rats and proteome analyses of their pituitaries

Di-(2-ethylhexyl)phthalate (DEHP) is a plasticizer and a ubiquitous environmental contaminant that may have adverse effects on human reproductive health. We examined the long-term exposure effects of DEHP on female rats and observed a strong effect on estrous cyclicity that produced a continuous diestrous stage. We found that the serum estradiol, follicle-stimulating hormone (FSH), pituitary FSH and luteinizing hormone levels were significantly reduced in the treated rats. To examine on the endocrine disrupting effects, we performed proteome-based analyses of their pituitaries, and found two proteins with remarkably reduced their levels. They were identified as the valosin-containing peptide/p97 (VCP/p97) and UMP-CMP kinase and their average protein spot intensities on statistical analysis of the spots differences of the treated/control rats were 0.13 and 0.21, respectively. Furthermore, there were 14 other proteins that had significantly changed levels, and their average protein spot intensities were in a range of 0.26 to 0.50 in 13 proteins and 2.74 in one. The reduction of in level of 7 proteins seems to be related to the intracellular protein transporting pathway, and it appears to suggest a slow down of gonadotrophin-releasing capability. Reduction of gonadotrophin release in the pituitary seems to lead to a decrease of serum estradiol level and continuous diestrous stage in estrous cyclicity.     

The anorectic effect of fenfluramine is influenced by sex and stage of the estrous cycle in rats

The controls of food intake differ in male and female rats. Daily food intake is typically greater in male rats, relative to female rats, and a decrease in food intake, coincident with the estrous stage of the ovarian reproductive cycle, is well documented in female rats. This estrous-related decrease in food intake has been attributed to a transient increase in the female rat's sensitivity to satiety signals generated during feeding bouts. Here, we investigated whether sex or stage of the estrous cycle modulate the satiety signal generated by fenfluramine, a potent serotonin (5-HT) releasing agent. To examine this hypothesis, food intake was monitored in male, diestrous female, and estrous female rats after intraperitoneal injections of 0, 0.25, and 1.0 mg/kg D-fenfluramine. The lower dose of fenfluramine decreased food intake only in diestrous and estrous females, suggesting that the minimally effective anorectic dose of fenfluramine is lower in female rats, relative to male rats. Although the larger dose of fenfluramine decreased food intake in both sexes, the duration of anorexia was greater in diestrous and estrous female rats, relative to male rats. Moreover, the magnitude of the anorectic effect of the larger dose of fenfluramine was greatest in estrous rats, intermediate in diestrous rats, and least in male rats. Thus our findings indicate that the anorectic effect of fenfluramine is modulated by gonadal hormone status.     

Maternal Coordination of the Daily Rhythm of Malate Dehydrogenase Activity in Testes from Young Rats: Effect of Maternal Sympathetic Denervation of the Pineal Gland and Administration of Melatonin

Chronic sympathetic denervation of the pineal gland by bilateral removal of the superior cervical ganglia (SCG) was performed on female rats 30 days before impregnation. The offspring, maintained in the dark from birth, had disruption of the malate dehydrogenase circadian rhythm in the testes at 25 days of age. A daily injection of melatonin (1 mg/kg s.c. at 10:00 or 18:00 h) to denervated mothers from the 14th day of pregnancy up to the 10th day postpartum produced one daily phase in the enzyme activity of testes in the offspring. Entrainment of daily enzyme activity also was obtained when the hormone was administered orally to the pups during the postnatal period or when pups were reared by intact (not denervated) foster mothers. The results indicate the involvement of the maternal pineal gland in the maternal transfer of photoperiodic information necessary for the coordination of the circadian system in young rats.     

Maternal Coordination of the Daily Rhythm of Malate Dehydrogenase Activity in Testes from Young Rats: Effect of Maternal Sympathetic Denervation of the Pineal Gland and Administration of Melatonin

Chronic sympathetic denervation of the pineal gland by bilateral removal of the superior cervical ganglia (SCG) was performed on female rats 30 days before impregnation. The offspring, maintained in the dark from birth, had disruption of the malate dehydrogenase circadian rhythm in the testes at 25 days of age. A daily injection of melatonin (1 mg/kg s.c. at 10:00 or 18:00 h) to denervated mothers from the 14th day of pregnancy up to the 10th day postpartum produced one daily phase in the enzyme activity of testes in the offspring. Entrainment of daily enzyme activity also was obtained when the hormone was administered orally to the pups during the postnatal period or when pups were reared by intact (not denervated) foster mothers. The results indicate the involvement of the maternal pineal gland in the maternal transfer of photoperiodic information necessary for the coordination of the circadian system in young rats.     

Progesterone inhibits, on a circadian basis, the release of melatonin by rat pineal perifusion

The effects of 10(-6) and 10(-9) M of progesterone were documented on isoproterenol-stimulated melatonin release by perifused pineal glands removed from female rats in diestrous at two different times of a 12 : 12 h light/dark cycle, 7 and 19 h after light onset (which corresponds to daytime and nighttime, respectively), to look for the existence of a circadian stage-dependence of the hormone effects. Three weeks before the experiment, the rats were synchronized with a 12 : 12 lighting regimen. Progesterone decreased by approximately 50% the release of melatonin during the light span, but not during the dark span. These results show the direct effects of this ovarian hormone on pineal melatonin release and strongly suggest a time-related effect of progesterone on pineal function.     

Effect of neonatal melatonin administration on sexual development in the rat

In order to study the mechanisms by which melatonin modulates sexual development, 5-day-old female Wistar rats have been treated with a single s.c. injection of melatonin, 3 h before the darkness onset. Criteria for sexual development were the age of vaginal opening and the circulating levels of prolactin, LH, FSH and estradiol. Also, pineal melatonin content was measured. There was a precocious puberty (P less than 0.01) in melatonin-treated rats measured by the age of the vaginal opening. An increase in the number of estrous smears over the whole period studied was observed in melatonin-treated animals as compared to controls. Along with these modifications, there was decrease in pineal melatonin content and serum prolactin levels, on day 21 of life (P less than 0.05), with an increase in both parameters on day 30 of age, in melatonin-treated rats as compared to controls, with no modifications at any other time studied. No differences were detected for serum LH levels considering the whole period studied for both groups. There was a faster decrease in plasma FSH levels with age in melatonin-treated animals than in controls. Serum estradiol levels were decreased in the peripubertal period in melatonin-treated rats as compared to controls. All these data suggest that the modifications induced by neonatal melatonin administration on prolactin, FSH and estradiol could be responsible for the precocious puberty shown in this study.     

Effects of larval tapeworm (Taenia taeniaeformis) infection on reproductive functions in male and female host rats

This report examined the effects of larval tapeworm infection on the reproductive functions in both male and female host rats. Female rats were matched by age, then randomly assigned to control and treatment groups (infected with larval tapeworms). Estrous cycles were determined by vaginal smear with 95% of the control group exhibiting 4-day normal cyclicity and only 55% of the treated group exhibiting normal cycles. Female fertility was then evaluated for the normally cycling rats based on the percentage of successful matings on the evening of proestrus, number of implantation sites on Day 8 of pregnancy, and number of pups born at term. The normally cycling rats exhibited 96% successful mating, 12.95 +/- 1.80 implantation sites, and 11.20 +/- 1.80 pups born. Five months after larval tapeworm infection, the fertility parameters were decreased to 79%, 9.10 +/- 1.20, and 7.50 +/- 1.50, respectively. The control females were then used in a study of male fertility after larval tapeworm infection employing the same parameters used to test female fertility. At the onset of the study, control groups exhibited 95% successful mating, 12.50 +/- 1.50 implantation sites, and 11.60 +/- 1.60 pups born at full term. After the 5-month infection period, the parameters were substantially reduced to 29%, 6.20 +/- 0.80 implantation sites, and 5.10 +/- 0.80 pups, respectively. Average testosterone concentrations in serum and testis from control male rats were 8.80 +/- 0.95 ng/ml and 3.88 +/- 0.25 ng/mg protein, respectively. After the 5-month infection period, these levels were reduced to 2.47 +/- 0.31 ng/ml and 1.28 +/- 0.12 ng/mg protein, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Orienting behavior of female white rats in estrus cycle and its dependence on handling

Characteristics of orienting behavior of intact and handled female white rats were studied in the "open field" test. Experimental group of animals were formed according to stages of estrous cycle: (1) diestrus, (2) proestrus, (3) estrus, and (4) metestrus. The stage of the cycle was determined by vaginal smears. Over the period of 10 days rats were handled daily for 5 minutes. No behavioral changes over the course of estrous cycle were found in intact rats. Handling revealed some behavioral features related to the levels of steroid hormones in reproductive cycle. Most prominent changes in orienting behavior were observed at transition from estrous to metestrous. At the stage of estrous motor activity was maximal and grooming was minimal. The maximal contrast in the structure of orienting behavior was observed between estrous and diestrous stages.     

Estrous cyclicity and reproductive success are unaffected by translocation for the formation of new reproductive pairs in captive red wolves (Canis rufus)

This study investigated possible female-related causes for inconsistent success among reproductive pairs in the zoo-based red wolf (Canis rufus) population. Females (n = 13) at seven institutions were assessed for evidence of ovulation and normal reproductive cycles through the measurement of estradiol and progesterone metabolite excretion in feces. Fecal cortisol metabolites (FCM) were also measured. Factors potentially affecting FCM and/or estrous cyclicity were recorded, including exhibit status (on vs. off), reproductive history (proven vs. unproven), copulatory behaviors (ties observed: yes or no), pregnancy/parturition (pups or no pups produced), and translocation before the observed breeding season (yes or no). No differences were observed in baseline FCM between females housed on versus off-exhibit (p = .46) or between females producing pups and those who did not (p = .19). Baseline FCM were significantly lower among females observed in copulatory ties compared to females never observed in a tie (p = .04), and tended to be higher in females translocated before the breeding season compared to females in existing reproductive pairs (p = .11), and among historically unproven females compared to proven females (p = .11). All females evaluated had an endocrine profile indicative of ovulation and among the four females translocated to be paired with a new male before the breeding season, two had successful pregnancies, producing litters. Therefore, despite observed differences in baseline FCM among factors, estrous cyclicity and reproductive success are unaffected by translocation for the formation of new reproductive pairs in the zoo-based red wolf population.     

Early treatment of young female rats with progesterone delays the aging-associated reproductive decline: a counteraction by estradiol

We have recently reported that successive treatments of young virgin rats with progesterone (P) implants produce elevated circulating P and consistently low estradiol (E2) concentrations, and subsequently delay the aging-associated reproductive decline. Inasmuch as E2 has been implicated in causing the loss of regular estrous cyclicity in aging rats, the present study examined if the concomitant presence of moderately increased circulating E2 levels could counteract the effects of P implants on reproductive aging. Starting at 3 1/2 mo and continuing to 8 mo of age, regularly cyclic, virgin rats received either s.c. Silastic implants of P (P-implanted), blank Silastic implants (virgin controls), or P + E2 implants (P + E2-implanted) for 3 wk, followed by implant removal for 1 wk. Each of these implant treatments was repeated in the same female rats 5 times. Blood samples were obtained on different days of the estrous cycle from the control group and on Day 11 of successive treatments with P or P + E2 implants for measurements of serum P and E2 values. At 8 1/2 and 10 mo of age, estrous cyclicity of these same virgin rats was again monitored, and 10-mo-old regularly cyclic females from each treatment group were mated with young fertile males to complete term pregnancies. While virgin controls showed cyclic increases in E2 and P secretion during the estrous cycle, P-implanted virgins exhibited consistently low serum E2 and moderately increased P levels during 5 successive treatments. The latter indicates a potent inhibition of ovarian E2 secretion by P implants.(ABSTRACT TRUNCATED AT 250 WORDS)     

The relation of ovarian steroid levels in young female rats to subsequent estrous cyclicity and reproductive function during aging

In multiparous rats, the incidence of regular estrous cyclicity and fertility decreases markedly at middle age. However, recent studies have shown that repeated pregnancies or progesterone (P) implants can subsequently cause retired breeder females to maintain regular cyclicity for an extended period of time; these results suggest a P-mediated deceleration of reproductive aging. In the present study, we examined the relation of ovarian steroid levels in young virgin females to their subsequent estrous cyclicity and reproductive function during aging as compared to multiparous females. Beginning at 4 mo of age and continuing to 6 mo of age, regularly cyclic virgin rats received either consecutive P implants (n = 41) or no implants (controls, n = 45) for 3 wk, followed by implant removal for 1 wk. Additional females (n = 72) were mated and allowed to undergo repeated pregnancies at 4, 6 1/2, and 8 mo of age. Blood samples were obtained throughout the estrous cycle (virgin females), during pregnancy (multiparous rats), and on Day 11 of successive treatments with P implants (virgins with P implants) for P, estradiol (E2), and testosterone (T) measurements. Subsequently, regularly cyclic females from all three groups were mated with fertile males to undergo term pregnancies at 10 and 12 mo of age. While the virgin controls showed cyclic increases in P, T, and E2 secretion during their estrous cycles, the P-implanted females had persistently low E2 and high P and T levels during treatment, which indicates an inhibition of ovarian E2 synthesis by P.(ABSTRACT TRUNCATED AT 250 WORDS)     

Proestrous hormonal changes preceding the onset of ovulatory failure in lightly androgenized female rats

Proestrous hormonal profiles were characterized in lightly androgenized female rats prior to the onset of the delayed anovulatory syndrome (DAS). In these females, ovulatory failure and persistent vaginal estrus (PVE) occur at a very early age. Female Sprague-Dawley rats were injected with 10 micrograms testosterone propionate (TP) on postnatal Day 5. Control rats were untreated. All animals were weaned at 21 days of age, and following the onset of puberty, estrous cyclicity was monitored by vaginal smear. Rats showing regular 4-day cycles were used. Between 50-70 days of age, intra-atrial cannulae were implanted on a morning of proestrus (0700-0900 h) and blood was sampled at 2-h intervals from 1000 to 2000 h. Additional samples were taken at 0.5-h intervals from 1600 to 1800 h. Plasma was assayed for luteinizing hormone (LH), follicle-stimulating hormone (FSH) and progesterone (P) by radioimmunoassay (RIA). All animals were monitored for the onset of PVE or other alterations in estrous cyclicity. Females treated neonatally with TP that subsequently showed PVE by 150 days of age (PRE DAS) displayed a reduced peak amplitude (P less than 0.01) and delay in onset (1600 vs. 1400 h) of LH but not FSH secretion, when compared to controls. Females treated neonatally with TP that did not enter PVE by 150 days of age (No DAS) also showed a delayed rise in LH when compared to controls. However, the amplitude of LH secretion was not different from controls or PRE DAS females.(ABSTRACT TRUNCATED AT 250 WORDS)