Luteinizing hormone response to controlled-release deslorelin in estradiol benzoate primed ovariectomized gilts

Development of a controlled release formulation of gonadotropin releasing hormone that would stimulate a LH surge capable of reducing the time span of ovulations would greatly benefit reproductive management because a single timed insemination could be used. A dose-response study was conducted to determine if Deslorelin, a potent gonadotropin releasing hormone analogue, delivered via the SABER system, a biodegradable controlled release system, would stimulate an ovulatory-like LH surge in the pig. Twenty ovariectomized gilts, approximately 200 d old and 100 kg body weight (BW), received estradiol benzoate (15 microg/kg BW im) and 48 h later, the gilts were given deslorelin at 0, 12.5, 25.0, 50.0 or 100.0 microg im (n = 4 each treatment group). Compared to controls, mean blood deslorelin concentrations were still elevated at 30 h after deslorelin. Mean deslorelin magnitude, area under the curve and duration were sequentially greater (P<0.05) in a dose-dependent sequence. Compared to controls, serum LH concentrations were elevated (P<0.05) for 6 to 12 h after deslorelin. A dose-response relationship was absent for all parameters of LH secretion. Magnitude of the serum LH response was greatest (P<0.05) in the 12.5 microg and 50.0 microg groups, whereas area under the curve was lower (P<0.05) after 25.0 microg of deslorelin than after 12.5, 50.0 and 100.0 microg, which were not different from each other. Thus, no more than 12.5 microg of deslorelin is necessary to obtain maximum LH release in the model studied and doses less than 12.5 microg may also be effective.     

Gonadotropic and ovarian hormone response in dairy cows treated with norgestomet and estradiol valerate

Injection of estradiol valerate in conjunction with receiving a norgestomet ear implant (Syncro-Mate-B) reduced plasma progesterone (P<.001) and FSH (P<.02) and increased estradiol (P<.01) in postpartum cows during the treatment period. Occurrence of LH and FSH peaks (P<.05) varied between 12 and 48 hr follwing removal of SMB implants and estrous behavior was minimal. FSH was strongly correlated to LH and was inversely related to progesterone in untreated cows and to estradiol in treated cattle. Syncro-Mate-B suppressed luteal activity and peak gonadotropin release during treatment and elicited variable endocrine and behavioral response following treatment.     

Effect of treatment with progesterone and oestradiol benzoate on ovarian follicular turnover in postpartum anoestrous cows and cows which have resumed oestrous cycles.

Two experiments were carried out to determine the effect of a low dose of progesterone (P) with and without the addition of an injection of oestradiol benzoate (ODB) on ovarian follicle dynamics, oestradiol production and LH pulsatility in postpartum anoestrous cows, compared with cows which had resumed oestrous cycles (cycling cows). In the first experiment, anoestrous Jersey cows were treated with (AN+P, n=8) or without (AN-3, n=3) a previously used intravaginal progesterone releasing (CIDR) device for 10 days, commencing 3 or 4 days after emergence of a new dominant follicle (DF1) as determined by transrectal ultrasonography. Contemporary cycling cows (CYC+P, n=8) were similarly treated with used CIDR devices and injected with prostaglandin F(2alpha) (PGF) at the time of device insertion. Follicle turnover was monitored by daily ultrasonography and pulsatile release of LH was measured on the ninth day after device insertion. During the period of CIDR device insertion, a second dominant follicle emerged in 4/8 of the CYC+P group and 7/8 of the AN+P group (P=0.14). Maximum diameter of DF1 was greater in cows in the CYC+P compared with the AN+P group (P=0.02), but did not differ between cows in the AN+P and AN-P groups (P>0.1). Frequency of LH pulses was greater in cows in the CYC+P than AN+P group (P=0.06), and in cows in the AN+P than AN-P group (P=0.02).In the second experiment, anoestrous (n=20) and cycling (n=11) Friesian cows were treated with a new CIDR device for 6 days commencing 3 days after emergence of a new dominant follicle (DF1). Cycling cows were also injected with PGF on the day of device insertion. Half of the cows in each group were injected with 2mg ODB on the day of device insertion. Daily ultrasonography was used to monitor follicular dynamics throughout the experimental period. Follicular turnover was increased by ODB in cycling (5/5 versus 1/6; P<0.05), but not anoestrous cows (5/9 versus 4/11). Persistence of DF1 was reduced by ODB treatment in both cycling and anoestrous cows (P<0.001). Maximum diameter of DF1 was influenced by ODB treatment and reproductive status (P<0.05). In anoestrous cows in which a second dominant follicle did not emerge during the period of device insertion, the interval from emergence of DF1 to emergence of a second dominant follicle was significantly delayed by treatment with ODB (P=0.04).In conclusion, P treatment of anoestrous cows increased pulsatile release of LH, but did not induce the development of persistent follicles. Injection of ODB in association with P treatment reduced the persistence of dominant follicles in both cycling and anoestrous cows, but delayed subsequent follicular development in a proportion of anoestrous cows.     

Gonadotropin releasing hormone treatment of dairy cows with ovarian cysts. I. Gross ovarian morphology and endocrinology

Dairy cows diagnosed as having ovarian cysts were assigned to receive either sterile water or 100 mug GnRH (5 cows/group). Immediately prior to treatment and three days post-treatment, ovaries were observed via paralumbar laparotomy, photographed and visible structures and ovarian size recorded. Nine to thirteen days post-treatment, ovaries were removed. Blood plasma was collected for hormone determinations prior to each surgery, 1.5 and 3.0 hours and 1, 5 and 9 days post-treatment. Although concentrations were similar between groups prior to treatment, concentrations of progesterone were higher and LH and estradiol-17beta lower for GnRH treated cows than control cows, immediately prior to ovariectomy. A layer of luteal tissue approximately 5 mm thick was present around the periphery of the cystic structure at ovariectomy in 4 of 5 GnRH treated cows, but in only one control cow. The thickness of the luteal layer around the periphery of the ovarian cysts was correlated -.82, .78 and -.63 with estradiol-17beta, progesterone and LH, respectively. In summary, response to GnRH treatment in cows with ovarian cysts appears to be characterized in most cases by luteinization of the cystic structures.     

Effect of days postpartum and exogenous GnRH on reproductive hormone and ovarian changes in postpartum suckled beef cows

Two experiments were conducted to determine the effect of days postpartum and exogenous gonadotropin releasing hormone (GnRH) on reproductive hormone and ovarian changes in postpartum suckled beef cows. In experiment 1, eight suckled cows were bled at .5 hour intervals for 4 hours on days 7, 14, 21 and 28 postpartum. Although mean concentrations of plasma luteinizing hormone (LH) were positively correlated with days postpartum, mean concentrations did not differ. The mean maximum change and the variance of plasma LH were low on days 7, 14, 21 and 28 postpartum. Although the number of cows with an ovarian follicle and follicular size increased with days postpartum, mean concentrations of estradiol-17beta did not change. The interval from parturition to the first detected ovarian follicle and the first postpartum estrus was 17.5 +/- 2.6 days and 36.0 +/- 2.2 days, respectively. An elevation in plasma progesterone was detected about one week prior to the first postpartum estrus in 6 of the eight cows in the absence of corpora lutea. In experiment 2, gonadotropin releasing hormone (GnRH) induced ovulation in 4 of the 8 cows treated on day 27, 28 or 29 postpartum whereas none of the 8 saline treated cows ovulated to treatment. The interval from parturition to first estrus and conception were similar for both groups (P >.10).     

Risk factors for postpartum ovarian cysts and their spontaneous recovery or persistence in lactating dairy cows

Cystic ovarian disease is a major cause of reproductive failure and economic loss for the dairy industry. Many cysts that develop during the early postpartum period regress spontaneously. However, it is difficult to decide at what point it would be more cost effective to treat ovarian cysts than to wait for spontaneous recovery. The objective of this study was to analyze risk factors for the development of the ovarian cystic condition during early and late postpartum, and for its persistence or recovery during the pre-service period in lactating dairy cows. Using multiple logistic regression, we analyzed data derived from 873 lactating dairy cows from a single herd. An ovarian cyst was diagnosed if it was possible to observe a single follicular structure with an antrum diameter > or = 25 mm in the absence of a corpus luteum in three sonograms performed at 7-day intervals. The cystic condition was denoted as early if the cyst was diagnosed 43-49 days postpartum, and late if detected 57-63-day postpartum. Spontaneous cyst regression before 60-day postpartum was regarded as early cystic recovery. For the early cystic group, there were no significant effects of lactation number, body condition score on prepartum Day 60, at parturition or on postpartum Day 30, or of body condition loss from parturition to 30-day postpartum. Cows calving in summer were 2.6 times more likely to develop ovarian cysts than those giving birth in winter. The risk of having a cyst was 1.9 times higher in cows with an abnormal puerperium. A 1-kg increase in milk yield raised the risk of cysts by a factor of 1.05. A 1-unit increase in body condition score (scale from 1 to 5) from prepartum Day 60 to parturition increased the risk of cyst development 8.4 times. Milk production and lactation number were negatively correlated with spontaneous early cyst recovery. A 1-kg decrease in milk production increased the probability of cyst recovery by a factor of 1.06, and a 1-unit drop in lactation number was associated with a 1.4-fold increased probability of cyst recovery. For the late cystic group, there were no significant effects of abnormal puerperium and body score data, except for a prepartum change in body score. Calving season (Odds ratio: 2.3), lactation number (Odds ratio: 1.36), increased milk production (Odds ratio: 1.05) and increased body condition score during the prepartum period (Odds ratio: 4.3) were all related to an increased risk of ovarian cysts. The probability of having a late cyst was 36.6 times greater in cows with early cysts. These findings suggest that it would be profitable to treat multiparous cows having cysts very early in the postpartum period, while treatment of primiparous cows should be delayed, at least until the end of the pre-service period, to provide the opportunity for spontaneous recovery.     

Hormone response of dairy cows with ovarian cysts after treatment with HCG or GnRH

Twenty lactating Holstein and Guernsey cows, diagnosed by rectal palpation as having ovarian cysts, were randomly divided within breed into two groups to receive either a single intramuscular injection of 100 μg of synthetic gonadotropin releasing hormone (GnRH) or an intravenous injection of 10,000 IU of human chorionic gonadotropin (HCG). The objective was to compare hormonal and clinical changes in cows with ovarian cysts following treatment with GnRH and HCG. Eight of ten and nine of ten cows given either GnRH and HCG, respectively, responded to treatment and subsequent fertility was not different between the two groups. Pre-injection plasma levels of LH, progesterone, and estradiol were highly variable. Mean plasma levels of LH, progesterone and estradiol did not differ between groups either following treatment (days 1–17 post-treatment), at the subsequent estrus, or during days 1–13 following the subsequent estrus. Mean LH levels did not differ significantly on the days either post-treatment or post-estrus except that levels were higher (P < .01) at the subsequent estrus as compared to the other days. Mean progesterone levels increased after treatment with either GnRH or HCG and were higher on days 5, 9 and 13 post-estrus and post-treatment as compared to the subsequent estrus. Mean levels of estradiol were higher (P < .05) at the subsequent estrus than any other time post-treatment or post-estrus. No other days were significantly different. In conclusion, GnRH and HCG are effective treatments for ovarian cysts in cattle. Endocrine response on days following treatment are similar for both compounds.     

Gonadotropin releasing hormone treatment of dairy cows with ovarian cysts: II. Histology of ovarian cyst walls

Dairy cows known to have ovarian cysts were assigned to receive either sterile water or 100 μg GnRH (5 cows/group). The ovaries were removed 9 to 13 days post-treatment and prepared for histologic study. The cyst walls of ovaries removed from cows following GnRH treatment were 2 to 15 times thicker than those from cows treated with water due to apparent luteinization of cells of theca interna. Following GnRH treatment, the cells in the outermost portion of the theca interna exhibited the greatest morphologic evidence of secretory activity whereas the innermost zone was hyalinized due to poor blood supply. The luteal cells in ovarian cystic cows treated with GnRH were similar to the small luteal cells in normal corpora lutea. In summary, GnRH treatment of cows with ovarian cysts appeared to induce luteinization of the cells in the outermost portion of the theca interna.     

Variability of ovarian structures and plasma progesterone profiles in dairy cows with ovarian cysts

Weekly reproductive health examinations were performed on 46 multiparous Holstein cows from 14 to 100 d post partum. Sixteen cows developed 19 nonsimultaneous ovarian cysts, with a mean day of first detection at 34.3 +/- 4.5 d post partum and a mean duration of 31.0 +/- 4.3 d after first detection. Coccygeal blood was collected three times weekly, and plasma progesterone concentrations were determined by radioimmunoassay. Cysts were diagnosed by palpation per rectum or by ultrasonography and classified as follicular or luteal cysts; the cows were not treated. Cows with a mean plasma progesterone concentration of < 1 ng/ml from the first day of detection (Day 1) of a cyst until Day 10 were classified as having a follicular cyst, and those with a mean plasma progesterone concentration of >/= 1 ng/ml from Day 1 to Day 10 were classified as having a luteal cyst. According to this classification, 58% of the cysts were follicular and 42% were luteal. There was an overall 47% agreement between classification by palpation and by ultrasonography on Day 1 with progesterone concentration during Days 1 to 10 after detection of the cyst. Detailed graphs of progesterone concentrations and area of largest follicles or cysts and corpora lutea demonstrate the variability of ovarian structures and progesterone profiles in cystic cows. Detection of a cyst at any one time accompanied by simultaneous measurement of progesterone can lead to different diagnoses of cyst type depending on the method of classification, the presence and age of luteinized tissue in the cyst and undetected corpora lutea.     

Comparison of progesterone-based protocols with gonadotropin-releasing hormone or estradiol benzoate for timed artificial insemination or embryo transfer in lactating dairy cows

The objective was to compare two protocols for synchronizing ovulation in lactating Holstein cows submitted to timed AI (TAI) or timed ET (TET). Within each farm (n = 8), cows (n = 883; mean ± SEM 166.24 ± 3.27 d postpartum, yielding 36.8 ± 0.34 kg of milk/d) were randomly assigned to receive either: 1) an intravaginal progesterone insert (CIDR^®) with 1.9 g of progesterone + GnRH on Day -10, CIDR^® withdrawal + PGF2α on Day -3, and 1 mg estradiol cypionate on Day -2 (treatment GP-P-E; n_TAI = 180; n_TET = 260); or 2) a CIDR^® insert + 2 mg estradiol benzoate on Day -10, PGF2α on Day -3, CIDR^® withdrawal + 1 mg estradiol cypionate on Day -2 (treatment EP-P-E; n_TAI = 174; n_TET = 269). Cows were subsequently randomly assigned to receive either TAI on Day 0 or TET on Day 7. Serum progesterone concentration on Day -3 was greater in GP-P-E than in EP-P-E (2.89 ± 0.15 vs 2.29 ± 0.15 ng/mL; P < 0.01), with no significant effect of group on serum progesterone on Day 7. Compared to cows submitted to TAI, those submitted to TET had greater pregnancy rates on Day 28 (44.0% [233/529] vs 29.7% [105/354]; P < 0.001) and on Day 60 (37.6% [199/529] vs 26.5 [94/354]; P < 0.001). However, there were no effects of treatments (GP-P-E vs EP-P-E; P > 0.10) on synchronization (87.0% [383/440] vs 85.3% [378/443]), conception (TAI: 35.3% [55/156] vs 33.8% [50/148]; TET: 50.7% [115/227] vs 51.3% [118/230]) and pregnancy rates on Days 28 (TAI: 30.5% [55/180] vs 28.7% [50/174]; TET: 44.2% [115/260] vs 43.9% [118/269]) and 60 (TAI: 27.2% [49/80] vs 25.9% [45/174]; TET: 38.8% [101/260] vs 36.4% [98/269]). In conclusion, GP-P-E increased serum progesterone concentrations on Day -3, but rates of synchronization, conception, and pregnancy were not significantly different between cows submitted to GP-P-E and EP-P-E protocols, regardless of whether they were inseminated or received an embryo.     

Luteinizing hormone release in intact and castrate rams is altered with immunoneutralization of endogenous estradiol

Changes in the dynamics of luteinizing hormone (LH) release in the adult ram following immunoneutralization of endogenous estradiol were investigated. Castrate rams were actively immunized against estradiol-6-bovine serum albumin for 7 months and then their patterns of episodic LH release and LH response to multiple injections of gonadotropin-releasing hormone (GnRH, two 5-micrograms doses given iv 2 h apart) were assessed (April). In comparison with control rams immunized against rabbit gamma globulin, estradiol-immunized rams (antibody titre approximately 1:5000) exhibited more frequent LH releases (11.7 +/- 0.3 vs. 9.3 +/- 0.8 pulses/8 h, P less than 0.05) and a greater LH response to the first GnRH injection (peak delta value 190 +/- 8 vs. 130 +/- 25 ng/mL, P less than 0.01). Estradiol antiserum collected from the castrate rams was used in the passive immunization of intact rams (antibody titre approximately 1:200) for 1 month (beginning mid-July). Although episodic LH release was always similar for control and immunized rams, testosterone levels in the latter group increased approximately 150%. In contrast with the castrate ram response, GnRH treatment (two 5-micrograms doses given iv 80 min apart) produced a "self-priming" effect on LH release in the intact rams, an effect that was dampened with estradiol immunoneutralization. Consequently, peak 2:peak 1 ratios for delta value and 80-min mean incremental increase were much smaller (P less than 0.01) for the immunized rams (approximately 2:1 vs. 4:1 for the control rams).(ABSTRACT TRUNCATED AT 250 WORDS)     

Prenatal melatonin influences developmental changes of tachykinins in response to estradiol benzoate

The developmental changes of hypothalamic, pituitary, striatum and pineal gland tachykinin concentrations, as well as the response to estradiol-benzoate (EB) administration, were studied in offspring of control and melatonin (MEL) treated mother rats. Female rats were studied throughout different phases of the sexual development: infantile, prepubertal and pubertal periods, in the four following groups; control-offspring+vehicle; control-offspring+EB; MEL-offspring+vehicle; MEL-offspring+EB. Hypothalamic NKA in control-offspring+ vehicle was significantly increased only at 27 days of age and in control-offspring+EB at 27 days of age and during the infantile period. Hypothalamic SP levels increased similarly in control-offspring+EB during the infantile period but the EB influence was more pronounced with significantly increased concentrations at 32 days of age. Prenatal melatonin treatment produced major alterations in these patterns of postnatal development. In MEL-offspring+EB tachykinins concentrations in the hypothalamus during infantile and prepubertal periods did not increase, however at 37 days of age, they showed significantly higher values than in control-offspring+EB groups. The developmental pattern of pituitary NKA and SP concentrations in both; control-offspring+vehicle and control-offspring+EB groups, showed similar values from the infantile period to puberty, indicating that NKA and SP concentrations remained at similar levels independently of the sexual stage, only at 27 days of age in control-offspring+EB significantly increased values were found as compared to MEL-offspring+EB. Prenatal melatonin did not produce marked modifications, only significantly lower NKA and SP concentrations in MEL-offspring+EB group were observed at 25 days of age in comparison to control-offspring+EB group. Striatal NKA and SP concentrations showed a similar developmental pattern. In control-offspring, EB treatment produced NKA and SP decreased concentrations at the infantile period than in control-offspring+vehicle and significantly increased concentrations during the prepubertal period, then during the pubertal period NKA and SP concentrations decreased in control-group+EB. However, prenatal melatonin treatment reduced the levels of striatal NKA and SP during the prepubertal period after EB treatment and delayed until pubertal period the increase previously observed in control group during the prepubertal period. In MEL-offspring+vehicle group striatal concentrations of both tachykinins remained at low levels from infantile period until pubertal period. Prenatal melatonin and EB did not produce major alterations in SP pineal concentrations throughout sexual development. Plasma estradiol concentrations were significantly higher in the groups that received EB treatment than in those that received vehicle during prepubertal and juvenile periods in control-offspring+EB group and during the pubertal period in MEL-offspring+EB group. These data indicate that prenatal MEL treatment may influence NKA and SP developmental pattern from the infantile period until adulthood in the female rat.     

Acute-phase response in dairy cows with acute postpartum metritis

The diagnostic value of 2 plasma acute-phase proteins, haptoglobin and alpha1-acid glycoprotein, and plasma N-acetyl-beta-D-glucosaminidase enzyme activity were studied in 29 newly calved dairy cows. Nineteen had developed acute metritis with putrid vaginal discharge within 2 wk after calving; 10 were clinically healthy controls. Plasma haptoglobin concentration remained low in most cows with acute postpartum metritis. Only the 3 most severely affected cows exhibited a strong haptoglobin response. These were later culled due to poor condition and reduced fertility. This suggests that in acute uterine infection a highly increased haptoglobin concentration indicates poor prognosis for repeat conception. Plasma alpha1-acid glycoprotein concentration increased in acute postpartum metritis, the response pattern being less prominent than that for haptoglobin. The alpha1-acid glycoprotein concentrations did not correlate with severity of disease, and, consequently, the capacity of alpha1-acid glycoprotein in differentiating genital infections was relatively poor. The highest alpha1-acid glycoprotein concentrations were detected in cows with retained placenta and/or dystocia. Plasma N-acetyl-beta-D-glucosaminidase activity levels did not differ between the cows with acute postpartum metritis and healthy control cows.     

Pituitary and ovarian responses of postpartum dairy cows to progesterone priming and single or double injections of gonadotropin-releasing hormone

Utilizing single or double pulses of gonadotropin-releasing hormone (GnRH), with or without progesterone pretreatment, we induced ovulation in dairy cows on day 14 postpartum. In experiment 1, neither progesterone priming nor repetitive injection of GnRH enhanced pituitary LH or FSH secretion compared to a single GnRH injection. However, pretreatment with 100 mg progesterone tended (P<0.1) to enhance luteal progesterone secretion during the induced cycle. We confirmed this observation in a second experiment by utilizing a larger number of cows. Cows given 100 mg progesterone prior to a single 200 mug injection of GnRH exhibited higher (P<0.05) concentrations of serum progesterone on days 12 and 16 of the induced cycle (days 26 and 30 postpartum). These results suggest that progesterone pretreatment may influence luteal progesterone secretion following ovulation. This appears to occur via an ovarian mechanism which is independent of pituitary gonadotropin secretion.     

Luteinizing hormone secretion as influenced by age and estradiol in the prepubertal gilt

The aim of this study was to determine if there is an age related reduction in the sensitivity of the negative feedback action of 17β-estradiol (estradiol) on luteinizing hormone (LH) secretion in the prepubertal gilt. Ovariectomized gilts at 90 (n=12), 150 (n=11) or 210 (n=12) days of age received estradiol benzoate (EB) osmotic pump implants 6/group and the remaining animals received vehicle control (C) implants except for 150-day C (n=5) on Day 0. On Day 10 blood samples were collected every 15 min for 8h and serum LH and estradiol concentrations were measured. Serum estradiol concentrations averaged 5 ± 1, 5 ± 1 and 7 ± 2 pg/ml for the 90-, 150- and 210-day-old gilts implanted with estradiol, respectively, whereas, serum estradiol concentrations was undetectable in C gilts. Mean serum LH concentrations, basal LH concentrations and serum LH pulse amplitude were less in EB-treated gilts at all ages compared to control animals. In contrast, LH pulse frequency initially was less in EB-treated gilts but subsequently increased (P<0.04) with age (from 0.8 ± 0.2 at 90 days to 5.2 ± 0.2/8h at 210 days), and at 210 days of age the pulse frequency was similar to C gilts. These results demonstrate an age related reduction in the sensitivity to the negative feedback action of estradiol on LH secretion and support the idea that the gilt conforms to the gonadostat hypothesis.     

Influence of season on estrous and luteinizing hormone responses to estradiol benzoate in ovariectomized sows

The objective of this experiment was to determine whether seasonal differences existed in estrous and LH responses to estradiol benzoate (EB) in ovariectomized sows. Sows were ovariectomized after weaning their first litter, and treatment was begun 120 d after ovariectomy. Sows were given 400 mug EB intramuscularly (i.m.) on July 24, 1982 (summer), October 24, 1984 (fall), January 29, 1985 (winter), and March 27, 1985 (spring). Beginning 24 h after EB, sows were checked for estrus four times daily. Proportion in estrus was affected by season, with all sows exhibiting estrus within 5 d after EB in summer, winter, and spring. Only three of five sows exhibited estrus within 5 d after EB in fall. Interval (h) to estrus was delayed in fall (80 h) compared to other seasons (62.6 h; SEM = 4.5). Concentrations of LH were suppressed within 6 h after EB in all seasons but rebounded to pre-injection levels more slowly in fall and spring than in winter and summer. Frequency of LH peaks (3.2 +/- .4 4 h ) was not affected by season, but amplitude (1.9 vs 0.9 ng/ml) and baseline (2.7 vs 1.6 ng/ml) were greater (P < 0.05) for summer than for the other seasons combined. At 6 h after injection, concentrations of estradiol-17beta (pg/ml) were greater in summer (58.3) than in fall (19.0), winter (32.4), or spring (16.6; SEM = 10.4). We conclude that environmental factors associated with season alter responsiveness of the brain to estradiol, thereby controlling sexual behavior and LH secretion.