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)     

Age-related alterations in pulsatile luteinizing hormone release: effects of long-term ovariectomy, repeated pregnancies and naloxone

Aging of the female reproductive system may be regulated by changes at the hypothalamic, pituitary, and ovarian levels. Long-term ovariectomy (LT-OVX) and/or multiple pregnancies delay age-related deterioration of several parameters of reproductive potential in rodents. We tested whether long-term suppression of cyclic ovarian hormone release that is normally associated with the 4- to 5-day estrous cycle decelerates age-related decreases in the frequency of luteinizing hormone (LH) pulses to assess whether hormonal milieu influences the rate of aging of the pulse generator. We determined the percentage of rats exhibiting pulsatile LH secretion, mean LH levels, and amplitude and frequency of LH pulses in seven groups of ovariectomized (OVX) rats. Young (3-4 mo), middle-aged (8-10 mo), and old (18-22 mo) virgin rats, ovariectomized 4 wk (4WK-OVX) prior to experimentation, were used to determine the effect of age. The effect of long-term ovarian hormone deprivation was tested by ovariectomizing rats at 2-3 mo of age and using them when they were middle-aged (8-10 months) or old (18-22 mo). The effect of deprivation of cyclic increases in ovarian hormones associated with repeated estrous cycles was tested by using retired breeder (RB) rats that had been ovariectomized 4 wk prior to experimentation. Each rat was implanted with a right atrial cannula and bled the next day at 10-min intervals for 3 h.(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)     

Role of decreased numbers of follicles on reproductive performance in young and aged rats

The primary objectives of this study were to: 1) determine if removal of 1.5 ovaries from young rats would mimic reproductive characteristics that normally occur with advancing age and 2) determine if removal of 1.5 ovaries from aged rats would further advance the process of reproductive aging. Removal of 1.5 ovaries increased the number of young (P less than 0.05) and old (P less than 0.01) rats that exhibited abnormal estrous cycles. In addition, concentrations of follicle-stimulating hormone (FSH) were higher at both ages in the groups with half an ovary. The increased concentrations of FSH are consistent with a decrease in the number of growing follicles after removal of 1.5 ovaries. All groups had lower concentrations of estradiol (E2) than young controls. There was a significant increase in the number of abnormal embryos with age and removal of 1.5 ovaries when rats were mated during a 5-day estrous cycle, but there was no effect if they were mated during a 4-day estrous cycle. From the results of this study, we conclude that the reduction in ovarian tissue in young and aged rats mimicked several reproductive characteristics of advancing age. Also, an effect of aging on the hypothalamus was evident in this study.     

Progesterone implants extend the capacity for 4-day estrous cycles in aging C57BL/6J mice and protect against acyclicity induced by estradiol

The onset of age-related acyclicity in rodents can be accelerated or attenuated by chronic treatment with estradiol (E2) or progesterone (P4), respectively. Because of the physiological effects of exogenous E2 and P4 on age-like reproductive changes, we sought to demonstrate if P4 could antagonize the acceleration of acyclicity by E2 in C57BL/6J mice. Mice were treated for 6 or 12 wk with P4 and/or orally administered E2. Twelve but not six weeks of E2 caused permanent acyclicity, whereas P4-treated mice had more 4-day cycles than did controls in both studies. The combination of E2 and P4 also caused a striking increase in 4-day cycles after treatment even greater than that from the P4 treatment alone. Thus, P4 transiently increases cycle regularity with a greater incidence of 4-day cycles and antagonizes the premature onset of acyclicity caused by chronic E2 treatment.     

Muscle activity and aging affect myosin structural distribution and force generation in rat fibers.

The purpose of this study was to determine whether increased muscle activity could reverse myosin structural alterations that occur in aged rat muscle and whether those alterations could be induced in young rat muscle by decreased activity. Semimembranosus muscle activity was increased by electrical stimulation (200-ms trains, 154 Hz, 5 V) through a nerve cuff on the tibial branch of the ischiatic nerve. The protocol consisted of 5 sets of 6-10 maximal isometric contractions performed twice per week for 4 or 8-10 wk. Decreased muscle activity was induced by denervation of the semimembranosus muscle for 2 or 4 wk. Semimembranosus fibers were then studied for Ca(2+)-activated force generation. Fibers were also spin labeled on the myosin catalytic domain and studied using electron paramagnetic resonance (EPR) spectroscopy to assess myosin structural distribution. Increased muscle activity for 4 and 8-10 wk in approximately 32-mo-old rats resulted in -16 and +4% changes in specific tension, respectively (P < 0.01). EPR spectra showed that the fraction of myosin heads in the strong-binding structural state during contraction was reduced at 4 wk (0.241 +/- 0.020 vs. 0.269 +/- 0.018, P = 0.046) but returned to normal by 8-10 wk (P = 0.67). Decreased muscle activity for 2 and 4 wk in approximately 9-mo-old rats resulted in 23 and 34% reductions, respectively, in specific tension; EPR spectra showed 16 and 35% decreases in strong-binding myosin (P < 0.01). These data support the hypothesis that changes in muscle activity affect muscle strength, at least in part through alterations in myosin structure and function.     

Effect of androstenedione on the oestrous cycle of the rat

The implantation of Silastic capsules containing androstenedione (release rate 63.2 +/- 4.4 micrograms/24 h) into 4-day cyclic rats resulted in a prolongation of the cycle (P less than 0.001), most rats showing 5-day cycles after the first, largely unaffected cycle. There was a reduction in ovulation rate (P less than 0.01) and lower serum LH levels on the morning of oestrus (P less than 0.01) but serum FSH levels were unaffected.     

Effects of hormone implants on estrus and ovulation in feral mares

Five groups of 30 captive feral mares each were implanted with silastic rods containing estradiol (E) and/or progesterone (P): E only with 8 g, P only with 24 g, P+HE with 8 g P + 8 g E, HP+E with 12 g P + 4 g E, HP+LE with 12 g P + 2 g E. Arbitrary group designations were differentiated by relative high (H) and low (L) amounts of steroid. Thirty mares received silastic rods containing no hormone (CI). Five mares from each group were bled every 2 wk for 4 mo and monthly for another 5 mo. All mares were tested for estrus by allowing them to stand in an alley between two pens of stallions and visually monitoring her response to the stallion. Serum P levels increased from 0.3 +/- 0.1 to 1.8 +/- 0.1 ng/ml in the P only group during the first 3 wk after implanting. Levels remained stable for the next 2 wk and then began a gradual decline. Serum P levels in the other groups were lower. Serum E levels were slightly increased in the groups receiving 8 g of E (E only and P+HE groups). Significantly fewer animals in the E only and P+HE groups exhibited estrus as compared with control animals (10 of 23 and 13 of 26 versus 22 of 25, respectively, P less than or equal to 0.003). However, animals receiving 24 g of P (P only) showed similar occurrences of estrus as controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Aging and respiratory muscle metabolic plasticity: effects of endurance training.

We examined the oxidative and antioxidant enzyme activities in respiratory and locomotor muscles in response to endurance training in young and aging rats. Young adult (4-mo-old) and old (24-mo-old) female Fischer 344 rats were divided into four groups: 1) young trained (n = 12), 2) young untrained (n = 12), 3) old trained (n = 10), and 4) old untrained (n = 6). Both young and old endurance-trained animals performed the same training protocol during 10 wk of continuous treadmill exercise (60 min/day, 5 days/wk). Compared with young untrained animals, the young trained group had significantly elevated (P less than 0.05) activities of 3-hydroxyacyl-CoA dehydrogenase (HADH), glutathione peroxidase (GPX), and citrate synthase (CS) in both the costal diaphragm and the plantaris muscle. In contrast, training had no influence (P greater than 0.05) on the activity of lactate dehydrogenase within the costal diaphragm in young animals. In the aging animals, training did not alter (P greater than 0.05) activities of CS, HADH, GPX, or lactate dehydrogenase in the costal diaphragm but significantly (P less than 0.05) increased CS, HADH, and GPX activities in the plantaris muscle. Furthermore, training resulted in higher activities of CS and HADH in the intercostal muscles in the old trained than in the old untrained animals. Finally, activities of CS, HADH, and GPX were significantly (P less than 0.05) lower in the plantaris in the old untrained than in the young untrained animals; however, CS, HADH, and GPX activities were greater (P less than 0.05) in the costal diaphragm in the old sedentary than in the young untrained animals.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pregnancy in young and aged rats: II. Peripheral serum progesterone concentrations

The concentrations of serum progesterone (P4) were determined in 3- and 11-mo-old female rats throughout pregnancy to determine if the subnormal ovarian formation of P4 from pregnenolone (P5), previously shown in vitro in the older rats, is accompanied by lower concentrations of P4 in the peripheral serum. Beginning on Day 11 of gestation and continuing throughout the remainder of pregnancy, 11-mo-old females exhibited a decline in the number of live fetuses and an increase in the number of dead fetuses. Between Days 1 and 8 of gestation, serum P4 concentrations were similar in young and aging females. Between Days 9 and 21 of gestation, serum P4 concentrations in aging rats that maintained pregnancy, or that exhibited fetal loss, were consistently greater than in the young animals. The normal or above-normal concentrations of serum P4, despite the subnormal ovarian formation of P4 demonstrable in vitro in 11-mo-old females during the first half of pregnancy, may reflect an alteration in the peripheral catabolism of P4 or no change in ovarian secretion of P4 in vivo. Despite the changes in ovarian steroidogenesis observed in vitro, pregnancy failure in aging female rats is not related simply to subnormal content of P4 in the peripheral circulation.     

Steroid receptor concentration in aged rat hindlimb muscle: effect of anabolic steroid administration.

Skeletal muscle is a target of anabolic steroid action; however, anabolic steroid's affect on aged skeletal muscle is not well understood. The effect of 4 wk of nandrolone decanoate (ND) administration on hindlimb muscles of 5- and 25-mo-old Fischer 344/Brown Norway rats was examined. ND (6 mg/kg body wt) was injected every 7th day for 4 wk. Controls received an oil injection. ND significantly reduced 25-mo-old rat perirenal fat pad mass by 30%. Soleus (Sol) and plantaris (Plan) muscle-to-body weight ratios were reduced in 25-mo-old rats. ND did not affect Sol or Plan muscle-to-body weight ratios at either age. Sol DNA concentration was reduced by 25% in 25-mo-old rats, and ND increased it to 12% greater than 5-mo-old rats. ND did not affect Plan DNA content. Sol androgen receptor (AR) protein in 25-mo-old rats was reduced to 35% of 5-mo-old values. ND increased AR protein by 900% in 25-mo-old rat Sol. Plan AR concentration was not affected by aging but was induced by ND in both age groups. Aging or ND treatment did not affect glucocorticoid receptor levels in either muscle. These data demonstrate that fast- and slow-twitch rat hindlimb muscles differ in their response to aging and ND therapy.     

Effectiveness of estradiol and progesterone in inducing LH release in different stages in rat estrous cycles

The effectiveness of estradiol (E2) and progesterone (P4) in inducing the release of the luteinizing hormone (LH) in the acutely ovariectomized (OVx) rats was studied. Female rats were Ovx in different stages of the estrous cycles and received a series of injections of E2 and P4. LH dynamic changes in the blood were examined in the afternoon of the following day after Ovx. Intact rats treated with oil vehicle or E2 and P4 were used as controls. The surgical operation and oil treatment did not interfere with the normal reproductive rhythm and LH secretion, but treatment with E2 and P4 did facilitate the LH release in some intact rats. E2 and P4 were very effective in inducing LH release in Ovx rats as compared with controls. Results indicated that E2 and P4 are essential substances in eliciting the LH surge, but their efficacies are dependent on the stage in the estrous cycles.     

Capability of ovarian steroids in inducing LH surges in acutely ovariectomized rats.

The capability of estradiol (E2) or E2 and progesterone (P4) in inducing luteinizing hormone (LH) surge in acutely ovariectomized (Ovx) rats was studied. In group I, rats were Ovx on estrus and were implanted with E2 capsules and atrial cannulae immediately after operation for blood samplings. In group II, rats were also Ovx on estrus but were implanted with E2 capsules and sampling cannulae the next day (the expected diestrus day 1, D1). In group III, rats were Ovx on D1, and were implanted E2 with capsules and atrial cannulae immediately after operation. All surgical operations were done around 1000h in the morning. On the expected diestrus day 2(D2) at 0930h, one half of the rats in each group received an oil vehicle or 2mg of P4 subcutaneously. Blood samples were taken from the indwelled cannulae at 1300, 1500, and 1700hrs in the afternoon. Results showed that P4 treatment amplified LH release in all three groups of rats primed with E2, and that the oil vehicle did not assist in LH release in E2 primed rats of group I and group II, but it did in 8 out of 10 rats in group III in the late afternoon of D2. Results suggested that the estradiol alone was capable in inducing LH surge on the expected D2 afternoon, and that under estradiol-primed conditions, P4 can trigger neural initiators to advance LH surge, but that the internal hormonal milieu at the time of ovariectomy may affect the influence of ovarian steroids in inducing LH release.     

Evidence that a decrease in testosterone negative feedback mediates the pubertal increase in luteinizing hormone pulse frequency in male ferrets

Neuroendocrine mechanisms regulating luteinizing hormone (LH) secretion during puberty were investigated in intact male ferrets and ferrets castrated at 8 wk of age that received s.c. implants of either empty or testosterone-filled Silastic capsules. To synchronize puberty onset among individuals, ferrets were exposed to short days between 8 and 16 wk of age, and then transferred to long days. Testis growth began in intact ferrets soon after photoperiod transition. Blood samples were obtained at 11, 15, 19, and 23 wk of age. LH pulse frequency was low in intact ferrets at 11 and 15 wk of age (less than or equal to 0.27 pulses/h), but rose to 0.94 pulses/h by 23 wk of age. No age-related increase in LH pulse frequency was observed in untreated castrated ferrets. LH pulses were rare in testosterone-treated castrated ferrets at 11 and 15 wk of age; but by 23 wk of age, frequency rose to 0.33 pulses/h. Thus, testis maturation in ferrets is accompanied by a dramatic increase in LH pulse frequency. No steroid-independent developmental increase in LH pulse frequency occurs in castrated ferrets. Furthermore, doses of testosterone that prevent LH secretion in young castrated ferrets do not as effectively suppress LH pulses in older ferrets. These data suggest that a decrease in the efficacy of testosterone negative feedback mediates the pubertal rise in LH pulse frequency in male ferrets.     

Glucoprivic regulation of estrous cycles in the rat

Previous research has shown that glucoprivation induced by chronic 2-deoxy-D-glucose (2DG) treatment extends estrous cycle length and disrupts reproductive behaviors in female hamsters, similar to food deprivation. Such treatment also suppresses food intake, which is reversed in male rats by reducing brain histamine levels prior to 2DG treatment. We, therefore, determined if 2DG extends estrous cycles in the female rat and if this is due to elevated brain histamine levels. We measured estrous cycle length during 2DG-induced glucoprivation, in the presence and absence of alpha-fluoromethylhistidine (FMH), a treatment that reduces brain histamine levels. Adult female rats were treated for 72 h with either saline (n = 8), 2DG (200 mg/kg S.C. every 6 h; n = 9), or FMH (100 mg/kg i.p. daily) + 2DG (200 mg/kg; n = 7). An additional group was treated with FMH (100 mg/kg i.p.; n = 5) alone. To determine if 2DG extends estrous cycles due to glucoprivation or to decreased caloric intake, a group of rats (n = 7) received a reduced diet equal to the mean daily food intake of rats receiving 2DG alone. 2DG induced more long estrous cycles compared to rats receiving saline, FMH + 2DG, or FMH alone. In rats treated with FMH + 2DG, the percentage of 4-5-day cycles was similar to that of saline-treated rats, and a high percentage of 4-5-day cycles was also observed in rats receiving a reduced diet. These data suggest that 2DG does not suppress estrous cycles through a decrease in total calorie intake, but rather by inducing glucoprivation. In addition, during 2DG-induced glucoprivation, elevated brain histamine levels contribute to the mechanism that suppresses reproductive function.     

Attenuation of force deficit after lengthening contractions in soleus muscle from trained rats.

The purposes of this study were 1) to determine the extent to which endurance training reduces the functional deficit induced by lengthening contractions in the soleus (Sol) muscle and 2) to determine whether young and old rats training at a comparable relative exercise intensity would demonstrate a similar protective effect from lengthening-contraction-induced injury. Young (3-mo-old) and old (23-mo-old) male Fischer 344 rats were randomly assigned to either a control or exercise training group [young control (YC), old control (OC), young trained (YT), old trained (OT)]. Exercise training consisted of 10 wk of treadmill running (15% grade, 45 min/day, and 5 days/wk) such that by the end of training the young and old rats were exercising at 27 and 15 m/min, respectively. After training, contractile properties of the Sol muscle were measured in vitro at 26 degrees C. The percent decrease in maximal isometric specific force (P(o)) was determined after a series of 20 lengthening contractions (20% strain from optimal muscle length, 1 contraction every 5 s). After the lengthening-contraction protocol, Sol muscle P(o) was decreased by approximately 26% (19.6 vs. 14.6 N/cm(2)) and 28% (14.8 vs. 9.6 N/cm(2)) in the YC and OC rats, respectively. After exercise training, the reduction in P(o) was significantly (P < 0.05) attenuated to a similar degree ( approximately 13%) in both YT rats (18.7 vs. 16.2 N/cm(2)) and OT rats (15.8 vs. 13.7 N/cm(2)). It is concluded that exercise training attenuates the force deficit after repeated lengthening contractions to a comparable extent in young and old rats training at a similar exercise intensity.     

A comparative study of adrenal progesterone secretion during the estrous cycles of hamsters and rats

Adrenal secretory rates and peripheral plasma levels of progesterone (PROG) were determined during the estrous cycles of hamsters and 4-day cyclic rats. In both species, the PROG concentrations in peripheral plasma were never more than 6% of those observed in adrenal venous plasma. In hamsters, adrenal PROG secretory rates varied from 3.8 ± 0.8 ng/min at 0800 hr on proestrus (P) to 8.5 ± 1 ng/min at 2000 hr on estrus (E). The rates noted on P were among the lowest observed and were similar to those noted at 0800 hr the following morning. In rats, adrenal PROG secretory rates varied from 57 ± 9 ng/min at 0800 hr on E to 130 ± 18 ng/min at 2000 hr on P. A significant decline occurred between 2000 hr on P and 0800 hr the following morning. Rats secreted 3 to 8 times more PROG than did hamsters when the secretory rates are expressed as ng/min/100 mg adrenal. In hamsters, the data suggest a relative lack of influence of female reproductive hormones on adrenal PROG secretion and in turn the latter may not be involved in reproductive hormonal changes leading to ovulation. In rats, the increased adrenal PROG secretion noted on P may be due to the influence of reproductive hormones on adrenocortical function. This elevated rate may in turn influence the hypothalamo-hypophyseal-ovarian axis.     

Diurnal pattern of proopiomelanocortin gene expression in the arcuate nucleus of proestrous, ovariectomized, and steroid-treated rats: a possible role in cyclic luteinizing hormone secretion

Opiate peptides are thought to modulate the pattern of LH release in female rats. We tested the hypothesis that changes in proopiomelanocortin (POMC) gene expression occur in proestrous (PRO) and ovariectomized (OVX) steroid-treated rats which may explain their unique patterns of LH secretion. Using in situ hybridization, we examined whether diurnal changes in POMC gene expression occur in the arcuate nucleus. Four groups of rats were used in this study. 1) PRO rats were used after exhibiting at least two consecutive 4-day estrous cycles; 2) OVX rats were killed 9 days after ovariectomy; 3) estradiol (E2)-treated rats were OVX for 7 days and then treated for 2 days; and 4) E2-progesterone (P4)-treated rats were treated with E2 as described above, and on day 9 at 1030 h, P4 was administered. Rats were killed at 2300, 0300, 1000, 1300, 1500, 1800, or 2300 h, beginning on the evening of diestrous day 2 or day 8 after ovariectomy. POMC gene expression exhibited a diurnal rhythm on PRO. Levels of mRNA rose during the morning, peaked between 0300-1000 h, and decreased by 2300 h. In E2-treated rats, which exhibited a LH surge similar in timing to the PRO surge, POMC mRNA levels exhibited a diurnal rhythm strikingly similar to that observed in PRO animals. OVX abolished the rhythm; however, average POMC mRNA levels across the 24-h period were not significantly different from those in PRO or E2-treated rats. P4 treatment increased POMC mRNA levels by 2300 h compared to those in all other experimental groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of exercise training on passive stiffness in locomotor skeletal muscle: role of extracellular matrix

The purpose ofthis study was to evaluate the effect of endurance exercise training onboth locomotor skeletal muscle collagen characteristics and passivestiffness properties in the young adult and old rat. Young(3-mo-old) and senescent (23-mo-old) male Fischer 344 rats wererandomly assigned to either a control or exercise training group[young control (YC), old control (OC), young trained (YT), oldtrained (OT)]. Exercise training consisted of treadmill runningat ~70% of maximal oxygen consumption (45 min/day, 5 days/wk, for 10 wk). Passive stiffness (stress/strain) of the soleus (Sol) muscle fromall four groups was subsequently measured in vitro at 26°C.Stiffness was significantly greater for Sol muscles in OC rats comparedwith YC rats, but in OT rats exercise training resulted in muscles withstiffness characteristics not different from those in YC rats. Solmuscle collagen concentration and the level of the nonreduciblecollagen cross-link hydroxylysylpyridinoline (HP) significantlyincreased from young adulthood to senescence. Although training had noeffect on Sol muscle collagen concentration in either age group, itresulted in a significant reduction in the level of Sol muscle HP in OTrats. In contrast, exercise had no effect on HP in the YT animals.These findings indicate that 10 wk of endurance exercise significantlyalter the passive viscoelastic properties of Sol muscle in old but notin young adult rats. The coincidental reduction in the principalcollagen cross-link HP also observed in response to training in OTmuscle highlights the potential role of collagen in influencing passivemuscle viscoelastic properties.

     

Delayed anovulatory syndrome induced by estradiol in female C57BL/6J mice: age-like neuroendocrine, but not ovarian, impairments

These studies describe induction of a delayed anovulatory syndrome (DAS) by estradiol (E2) in female C57BL/6J mice. Six days after birth, female mice were injected s.c. with 0.1 micrograms estradiol benzoate or oil. Over 90% of the oil-injected controls exhibited estrous cycles from 2 to 9 mo of age. In contrast, 60% of the E2-injected mice exhibited estrous cycles at 2 mo of age but were acyclic by 9 mo; these mice were considered to have exhibited a DAS, and had longer cycles than controls. At 12 mo, ovarian impairments were assessed by examining 1) ovulation after s.c. injection of 5 IU human chorionic gonadotropin (hCG), and 2) estrous cycles after grafting into young (3-mo-old) hosts. Simultaneously, neuroendocrine impairments were assessed by examining 1) the surge of luteinizing hormone (LH) induced by E2 implants after ovariectomy, and 2) estrous cycles after receiving ovarian grafts from 3-mo-old mice. Ovaries from DAS and control mice ovulated equally in response to hCG. Ovaries from DAS mice grafted into young ovariectomized hosts supported 30% more cycles, of shorter period, compared with ovaries from control donors. However, the E2-induced LH surge was 50% smaller in DAS mice than in controls. Ovariectomized DAS hosts with ovarian grafts from young mice supported 70% fewer estrous cycles, of longer period, compared with ovariectomized control hosts with young grafts. We conclude that the E2-induced DAS in female mice is not due to ovarian impairments, but seems to result from neuroendocrine impairments.