Evaluation of ultrasonography for monitoring follicular growth in rhesus monkeys

The purpose of this study was to determine if the ovaries and uterus of rhesus monkeys could be visualized by ultrasonography and to detect changes associated with follicular growth and ovulation. Animals were examined during 15 menstrual cycles, for an average of nine consecutive days. Ultrasonic recordings were correlated with hormonal parameters (estradiol 17beta, E(2); luteinizing hormone, LH; and progesterone, P) and laparoscopic findings. The uterus and both ovaries were observed in more than 90% of the examinations. A dominant follicle (DF) was identified during all ovulatory cycles, on average 1 d preceding the E(2) peak. The maximal diameter of the DF ranged from 3 to 7 mm. Laparoscopic examinations to determine the site of the DF confirmed ultrasonic findings in 10 of 14 cycles (P < 0.1). There was no significant difference in the size of the dominant and contralateral ovaries; however, more follicles with a diameter of 2 to 7 mm were found on the dominant ovary (P < 0.05). Two animals stimulated with exogenous gonadotropins showed a linear increase in ovarian size for 6 d prior to oocyte recovery (P < 0.05), reflecting an increase in the number of developing follicles. Ultrasonography can be used to identify the DF during spontaneous cycles in rhesus monkeys and to monitor the response of monkeys to exogenous gonadotropins.     

Post partum patterns of circulating FSH, LH, prolactin, estradiol, and progesterone in nonsuckling cynomolgus monkeys.

Circulating levels of FSH, LH, prolactin (Prl), estradiol (E), and progesterone (P) were determined by RIA in four intact and four monkeys luteectomized (CLX) at parturition in order to a) characterize the patterns of these hormones during the puerperium, and b) examine a possible inhibitory role of the "rejuvenated" corpus luteum (CL) on the resumption of follicle growth post partum. In both groups during the first four weeks, FSH and LH were at tonic levels typical of ovulatory cycles. Recurrent puerperal "surges" of FSH, but not LH, unaccompanied by increments in serum E, were observed in both intact and CLX monkeys. No consistent pattern of serum Prl was apparent. CLX was followed by a prompt fall in serum P levels, which were elevated above typical follicular phase levels into the second week post partum in intact monkeys. Menstrual cycles resumed 2-4 months after delivery. Hormonal patterns during the first menstrual cycle post partum were indistinguishable from those observed in pregravidic ovulatory cycles. The findings indicate that in nonsuckling cynomolgus monkeys a) although it secretes progesterone, the puerperal CL does not inhibit the resumption of the ovarian cycle post partum, b) the puerperal ovary is not absolutely refractory to gonadotropins, since initial trials with Pergonal + hCG stimulated ovarian function, and c) ovarian activity during the puerperium may be limited by factors other than the tonic supply of gonadotropins.     

Effects of ovarian tissue reduction on the menstrual cycle: persistent normalcy after near-total oophorectomy

These experiments were designed to evaluate whether removal of approximately 95% visible ovarian tissue would interrupt the short- or long-term regulation of cyclic ovarian function. On cycle Days 2 4 (onset of menses = Day 1), the entire left ovary and approximately 90% of the right ovary were removed from three cycling cynomolgus monkeys. After approximately 95% ovariectomy, there was an acute elevation of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which lasted 11 +/- 2 days. A midcycle-like gonadotropin surge occurred 20 +/- 3 days following approximately 95% ovariectomy; the next menses occurred 19 +/- 1 days later. Follicular phase patterns of estradiol preceded the midcycle gonadotropin surge, and luteal phase progesterone levels indicated subsequent ovulation. Two of three monkeys resumed normal menstrual cyclicity in the following cycle with follicular phase, luteal phase, and menstrual cycle lengths similar to pretreatment levels. Histological examination of the ovarian remnant removed on Day 21 of the next cycle revealed a morphologically normal corpus luteum and many small follicles. A second group of 6 rhesus monkeys also underwent approximately 95% ovariectomy for long-term evaluation of menstrual cyclicity; typical 28-day menstrual cycle patterns were observed in 4 of the 6 monkeys for 5 mo, with 2 of these 3 animals maintaining regular menstrual cycles for 1 yr. In summary, our data suggest that normal ovarian function, i.e. recruitment, selection, and dominance of the ovulatory follicle, ovulation, and subsequent corpus luteum function, is maintained with only approximately 5% of functional ovarian tissue remaining.(ABSTRACT TRUNCATED AT 250 WORDS)     

Menstrual cycle characteristics of seasonally breeding rhesus monkeys

Rhesus monkeys in seminatural environments exhibit a distinct seasonal mating cycle with conceptions restricted to the fall and winter months. In the present study, the characteristics of menstrual cycles were examined during a 1-year period in twelve rhesus monkeys in whom pregnancy was prevented. Menses occurred throughout the year, but ovulations were observed only in the fall and winter months. Menses in the spring and summer months occurred irregularly and were associated exclusively with anovulatory cycles. The total number of ovulations exhibited by these females during the breeding season ranged from two to six and was positively related to body weight, mean luteal phase progesterone (P) levels of normal cycles and social dominance rank. Ovulations with a short luteal phase were exhibited by four females (seven cycles), with the likelihood of occurrence increasing as the breeding season progressed. The incidence of abnormal cycles was predicted from the linear combination of parity, body weight and luteal phase P of normal ovulatory cycles. These results suggest that during the seasonally delimited period of ovulation, females exhibit a range in the quality and quantity of ovulations which may be predicted by certain idiosyncratic physical and behavioral traits.     

Relation between levels of circulating ovarian steroids and pituitary gonadotropin content during the menstrual cycle of the rhesus monkey

Anterior pituitary glands were removed from 27 intact cycling rhesus monkeys sacrificed in the early (Day 2), mid (Days 6--9) and late (Days 11--12) follicular phase, and in the early and late luteal phase (3--5 and 10--15 days after the midcycle luteinizing hormone (LH) surge). Assignment of cycle stage was confirmed by the pattern of circulating steroid and gonadotropin levels seen in the blood samples taken daily throughout the cycle. The anterior pituitary glands were weighed, stored at -30 degrees C and assayed for LH and follicle-stimulating hormone (FSH) content by specific radioimmunoassays. Serum estradiol levels and pituitary LH and FSH contents rose simultaneously during the follicular phase. After the preovulatory gonadotropin surge, pituitary LH content was low and invariant. Pituitary FSH content reached a nadir in the early luteal phase and tended to rise in the late luteal phase. Multiple correlation analyses revealed that there is a positive correlation between rising levels of estradiol in the circulation and pituitary LH (p = 0.003) and FSH (p = 0.017) content, and that there is a significant negative correlation between circulating progesterone levels and pituitary FSH content (p = 0.002). Pituitary LH content is less strongly related to circulating progesterone levels. There was no significant difference in the wet weights of the anterior pituitary glands during the five phases of the menstrual cycle studied.     

Changes in plasma estradiol, progesterone and LH level in the menstrual cycle of the adult female Japanese monkey during the mating season

Adult 15 female Japanese monkeys showing regular menstrual cycles were subjected to the daily blood sampling for the measurement of estradiol (E2), progesterone (P) and biological LH in the mating season. Monkeys were maintained under controlled conditions in a standardized environment. Of the 35 cycles observed, 18 (51.4%) were estimated as anovulatory cycles and 17 (48.6%) were ovulatory cycles. The anovulatory cycles were classified into three types according to the peak level of E2 (Type I: E2 less than 50 pg/ml 3 cycles, Type II: E2 less than 170 pg/ml 7 cycles, Type III: E2 greater than 170 pg/ml 8 cycles). The ovulatory cycles were classified into two Types according to the peak level of P (Type IV: P less than 5.0 ng/ml 5 cycles, Tyep V: P greater than 5.0 ng/ml 12 cycles). The menstrual cycle was 27.5 +/- 7.8 days. The differences between mid cycle LH surge and P level in Type IV and in Type V were statistically significant. It was revealed that female Japanese monkeys kept under controlled condition in the mating season showed high incidence of various types of anovulatory cycles and that the ovulatory cycles with low P elevation in the mid luteal phase showed low LH and P secretions on the mid cycle date.     

Seasonal modulation of luteinizing-hormone secretion in female rhesus monkeys

The seasonal restriction of ovulations in rhesus monkeys is thought to be due to enhanced estradiol (E2)-negative feedback suppression of luteinizing hormone (LH) during the spring and summer anovulatory months. This hypothesis was examined in seven ovariectomized monkeys housed in an outdoor environment and treated with various doses of E2 in a counterbalanced design during both the anovulatory season (May-Jul) and the breeding season (Sep-Nov). Subcutaneous implants of E2 produced levels that mimicked late follicular (LF-100 pg/ml) or periovulatory concentrations (PO-190 pg/ml). Analyses of twice weekly serum samples revealed that during the period of no E2 treatment (NT), basal levels of bioactive LH were significantly lower in the summer than the fall. Although treatment with both doses of E2 lowered basal LH levels during both seasons, the decrease in LH was significantly greater during the summer. Samples collected at 15-min intervals for 2 h revealed that during NT, LH pulses were significantly slower during the summer than in the fall, whereas pulse amplitude did not differ between seasons. Treatment with both doses of E2 either abolished or significantly reduced both LH pulse amplitude and frequency in the summer. In contrast, LH pulses during the fall were not affected by E2 treatment. Response to treatment with LH-releasing hormone (5 micrograms/kg i.v.) revealed that release was significantly reduced during E2 treatment in the summer. These data indicate that seasonal changes in the environment influence both nongonadal control and E2-negative feedback inhibition of LH secretion. The reduced ability of E2 to maximally suppress LH release in the fall can thus account for the seasonally delimited pattern of ovulations observed in rhesus monkeys.     

Lactation‐associated infertility in Japanese monkeys (Macaca fuscata) during the breeding season

To investigate the endocrine factors in Japanese monkeys (Macaca fuscata) responsible for the suppression of the estrous cycle during the first reproductive season after delivery (150–360 days postpartum), peripheral blood was taken to measure plasma concentrations of follicle stimulating hormone (FSH), luteinizing hormone (LH), progesterone, estradiol‐17β, immunoreactive (ir)‐inhibin, and cortisol. The results demonstrated that during the breeding season of lactating Japanese monkeys, circulating concentrations of FSH (1.7–2.7 ng/ml), LH (308.5–461.0 pg/ml), estradiol‐17β (<62.6 pg/ml), and progesterone (145.0–453.0 pg/ml) remained low and were similar to the nadir levels observed during both the normal menstrual cycles and the nonbreeding season. Concentrations of ir‐inhibin, which is secreted from both follicles and corpus luteum in female Japanese monkeys, were also low (300.5–585.0 pg/ml). This strongly suggests that no follicular development occurs during lactation. Serum concentrations of cortisol (261.0–519 ng/ml) were higher during lactation than during the nonbreeding season. Since babies were often seen suckling their mothers during the study, the results indicate that the increased cortisol levels were associated with suckling‐induced secretion of corticotrophin‐releasing hormone (CRH) and adrenocorticotropic hormone (ACTH). The results of this study indicate that a long period of postpartum infertility in lactating Japanese monkeys, with apparent inhibition of follicle growth and anovulation, is due to weak gonadotropin stimulation, which may occur as the result of a suckling stimulus. Zoo Biol 22:65–76, 2003. © 2003 Wiley‐Liss, Inc.     

Circadian profiles of progesterone,gonadotropins, cortisol and corticotropin in cycling and postmenopausal women

Little is known about the regulation of temporal variations of progesterone over the 24-hr span in young cycling women as well as in postmenopausal women. The purpose of the present study was to investigate the relationships between diurnal variations of progesterone and diurnal variations of hormones of the gonadotropic and corticotropic axes, and to provide further information on the source of progesterone secretion under physiological conditions. Twenty-four-hour hormonal profiles were explored under well-controlled laboratory conditions in 10 healthy women (21–36 yr old) with normal ovulatory cycles during early-mid follicular and late luteal phases, and in 8 healthy postmenopausal women (48–74 yr old). In young cycling women, significant positive relationships were found between progesterone and follicle-stimulating hormone (FSH) – but not luteinizing hormone (LH) – profiles during late luteal phase. Conversely, during follicular phase, significant positive relationships were evidenced between progesterone and cortisol profiles, but not between progesterone and FSH or LH. In postmenopausal women, strong positive correlations were found between progesterone and corticotropin (ACTH) or cortisol profiles. The present results indicate that during late luteal phase, temporal progesterone profiles are associated with FSH rather than with LH profiles. They also provide evidence that adrenal cortex is a major – or possibly the only – source of progesterone production during the follicular phase of the normal ovulatory cycle, and probably the only source after menopause.     

Influence of the hypothalamic-pituitary-adrenal axis on the menstrual cycle and the pituitary responsiveness to estradiol in the female rhesus monkey (Macaca mulatta)

In order to examine the effect of glucocorticoids on the menstrual cycle of rhesus monkeys, cortisol was injected twice daily during the follicular phase. This cortisol treatment did not alter basal gonadotropin secretion but blocked the normal follicular rise of estrogens, the gonadotropin surge and the luteal rise of progesterone, and delayed the onset of the next cycle. In a second study, estradiol benzoate (E2B) was injected on the sixth day following the start of menstrual bleeding either with or without concurrent adrenocorticotropic hormone (ACTH) treatment. E2B injection was able to stimulate surges of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) whether or not the animals had been treated with ACTH. These data suggest that, the action of cortisol, the final mediating step in the hypothalamic-pituitary-adrenal axis, occurs at the level of the gonads versus the pituitary in the rhesus monkey. While the pituitary response to endogenous gonadotropin-releasing hormone or exogenous E2B stimulation appears to remain unaffected, normal folliculogenesis is disrupted, preventing the follicular secretion of estrogens and the subsequent gonadotropin surges. The effects of corticosteroids are temporary, with normal cycling returning when plasma corticosteroids return to basal concentrations, albeit after a delay.     

Neuroendocrine changes in the aging reproductive axis of female rhesus macaques (Macaca mulatta)

Femalerhesus macaques show monthly menstrual cycles and eventually enter menopause at approximately 25 yr of age. To help identify early biomarkers of menopause in this nonhuman primate, we monitored reproductive hormones longitudinally from aged female macaques during the transitions from premenopause to perimenopause and postmenopause and found that, indeed, elevated plasma FSH was a better predictive factor of menopause onset than age. In a second experiment, we compared reproductive hormone profiles of young adult macaques (8-10 yr old) with those of regularly cycling old macaques (approximately 24 yr old). Indwelling vascular catheters were used for remote blood collection for at least 100 consecutive days, thereby covering three complete menstrual cycles in each macaque. Plasma levels of estradiol, progesterone, LH, FSH, follicular phase inhibin B, and anti-müllerian hormone (AMH) were determined during each menstrual cycle and were averaged for each animal; group mean differences were analyzed using one-way ANOVA. Old premenopausal macaques showed regular menstrual cycles that were qualitatively indistinguishable from those of young macaques; peak plasma levels of estradiol, progesterone, and LH were not significantly different. In marked contrast, peak plasma FSH concentrations were significantly higher, while inhibin B and AMH levels were generally lower, in the old premenopausal macaques compared with those in the young macaques. These data provide further evidence that rhesus macaques serve as an excellent model to study underlying mechanisms of human menopause. Furthermore, the data suggest that an age-related change in FSH, inhibin B, and AMH secretion may be the first endocrine manifestation of the transition into perimenopause, potentially having value in predicting the onset of the perimenopausal transition.     

Reproductive Behavior in the Rhesus Monkey: Social and Endocrine Variables

SYNOPSIS. Social groups of rhesus monkeys (Macaca mulatto) livingin outdoor environments exhibit a distinct seasonal mating patternand female rhesus are observed to be sexually receptive fordiscrete periods averaging about 9 days duration. In the laboratoryenvironment mating occurs throughout the year and, in the pairtest, female rhesus are observedto be sexually receptive throughall phases of a menstrual cycle, with a periovulatory peak incopulatorybehavior. The apparent conflict between results from field andlaboratory studies has been difficult to resolve because ofmethodological limitations inherent in each study environment.Studies conducted on social groups of rhesus monkeys housedin outdoor compounds, an environment in which the species typicalseasonal mating pattern is preserved and which allowsfor concomitantmeasurement of behavioral and hormonal variables, provided informationabout the covariance between female sexual behavior and ovariancycles. Female copulations were observed only in associationwith ovulatory cycles, and were limited to the follicular andperi-ovulatory phases of such cycles, demonstrating that copulatorybehavior in female rhesus monkeys is strongly influenced bycyclic hormonal variables. The studies also revealed that femalestend to conceive on the first ovulatory cycle of the season,that there was no synchrony of cycles among the females, andthat the best predictor of the timing of ovulation in a particularfemale is reproductive outcome in the previous year.     

Influence of ovaries and photoperiod on reproductive function in the mare.

A 16 h daily photoperiod hastened the onset of the ovulatory season (first ovulation); gonadotrophin and follicular changes prior to the onset were similar in intact light-treated and control mares. A preovulatory decline in FSH concentrations before the onset of the ovulatory season preceded the decrease in number of follicles (15--25 mm) and the rise in LH concentrations which was temporally associated with the growth of an ovulatory follicle. Seasonal changes of FSH and LH concentrations were found in ovariectomized mares and were influenced by photoperiod. During the anovulatory season, there was no ovarian influence on gonadotrophin concentrations. However, during the ovulatory season the ovaries exerted a positive influence on seasonally elevated LH concentrations during oestrus and a negative influence during dioestrus. The ovaries exerted a negative influence on seasonally elevated FSH concentrations throughout the oestrous cycle. The onset of the ovulatory season occurred at the time of the first sustained increase in LH concentrations resulting from positive seasonal (increasing photoperiod) and ovarian influences.     

Dynamics of circulating concentrations of gonadotropins and ovarian hormones throughout the menstrual cycle in the bonnet monkey: role of inhibin A in the regulation of follicle‐stimulating hormone secretion

In higher primates, increased circulating follicle‐stimulating hormone (FSH) levels seen during late menstrual cycle and during menstruation has been suggested to be necessary for initiation of follicular growth, recruitment of follicles and eventually culminating in ovulation of a single follicle. With a view to establish the dynamics of circulating FSH secretion with that of inhibin A (INH A) and progesterone (P₄) secretions during the menstrual cycle, blood was collected daily from bonnet monkeys beginning day 1 of the menstrual cycle up to 35 days. Serum INH A levels were low during early follicular phase, increased significantly coinciding with the mid cycle luteinizing hormone (LH) surge to reach maximal levels during the mid luteal phase before declining at the late luteal phase, essentially paralleling the pattern of P₄ secretion seen throughout the luteal phase. Circulating FSH levels were low during early and mid luteal phases, but progressively increased during the late luteal phase and remained high for few days after the onset of menses. In another experiment, lutectomy performed during the mid luteal phase resulted in significant decrease in INH A concentration within 2 hr (58.3±2 vs. 27.3±3 pg/mL), and a 2‐ to 3‐fold rise in circulating FSH levels by 24 hr (0.20±0.02 vs. 0.53±0.14 ng/mL) that remained high until 48 hr postlutectomy. Systemic administration of Cetrorelix (150 µg/kg body weight), a gonadotropin releasing hormone receptor antagonist, at mid luteal phase in monkeys led to suppression of serum INH A and P₄ concentrations 24 hr post treatment, but circulating FSH levels did not change. Administration of exogenous LH, but not FSH, significantly increased INH A concentration. The results taken together suggest a tight coupling between LH and INH A secretion and that INH A is largely responsible for maintenance of low FSH concentration seen during the luteal phase. Am. J. Primatol. 71:817–824, 2009. © 2009 Wiley‐Liss, Inc.     

Menstrual cycles in rhesus monkeys (Macaca mulatta) are unaffected by a single dose of the anesthetics ketamine and xylazine administered during the midfollicular phase at laparoscopy

To identify an anesthetic regimen that produces more complete relaxation and analgesia than ketamine hydrochloride (Ketaset®) alone, a combination of ketamine (15 mg/kg body weight) and the hypnotic xylazine (Rompun®, 0.33 mg/kg) was evaluated. Since the desired experimental application required that the anesthetic not interfere with normal hormonal events during the menstrual cycle, this combination administered on day 6 of the cycle was tested to determine whether hormonal surges, incidence of ovulation, or cycle length would be altered relative to the use of ketamine alone. In five of six animals, ketamine plus xylazine had no effect on the occurrence of timely surges of estrogen, luteinizing hormone (LH), or follicle-stimulating hormone (FSH), or on ovulation as determined by the presence of a corpus luteum at laparoscopy and normal serum concentrations of progesterone. There were no significant differences between the cycle during treatment and previous cycles in the same animal for length of the menstrual cycle (26.0 ± 2.3 [5] days; X? ± S.D. [n] or luteal phase (13.4 ± 2.4 [5] days). Likewise, these values did not differ from those of ten control monkeys treated with ketumine only on day 5 or 6 of the cycle (incidence of ovulation, 10/10; cycle length, 27.9 ± 1.8 [10]; luteal phase length, 15.1 ± 1.4 [10], P > 0.05). Patterns of circulating progesterone were not altered by the addition of xylazine anesthesia. These findings indicate that xylazine, given in the midfollicular phase, did not alter ovulatory events or menstrual cycle characteristics in rhesus monkeys. Ketamine plus xylazine apparently provides anesthesia appropriate for laparoscopy.     

Plasma inhibin A in heifers: relationship with follicle dynamics, gonadotropins, and steroids during the estrous cycle and after treatment with bovine follicular fluid

The relationship between follicle growth and plasma inhibin A, FSH, LH, estradiol (E), and progesterone was investigated during the normal bovine estrous cycle and after treatment with steroid-free bovine follicular fluid (bFF) to arrest follicle development. In the first study, four heifers were monitored over three prostaglandin (PG)-synchronized cycles. Blood was collected every 2-8 h, and ovaries were examined daily by ultrasonography. Inhibin A was measured using a modified enzyme-linked immunosorbent assay that employed a new monoclonal antibody against the alpha subunit of bovine inhibin. Plasma inhibin A ( approximately 50 pg/ml before luteolysis) rose steadily during the induced follicular phase (P < 0.05) to a peak ( approximately 125 pg/ml) coincident with the preovulatory E/LH/FSH surge. After ovulation, inhibin A fell sharply (P < 0.05) to a nadir ( approximately 55 pg/ml) coincident with the secondary FSH rise. During the next 3 days, inhibin A increased to approximately 90 pg/ml in association with growth of the new dominant follicle (DF). Plasma E also rose twofold during this period, whereas FSH fell by approximately 50%. Inhibin A was negatively correlated with FSH (r = -0.37, P < 0.001) and positively correlated with E (r = 0.49, P < 0.0001). Observations on eight cycles (two cycles/heifer), in which growth of the ovulatory DF was monitored from emergence to ovulation, showed that the first-wave DF (DF1) ovulated in three cycles and the second-wave DF (DF2) in five cycles. After PG, plasma inhibin A and E increased similarly in both groups, with concomitant falls in FSH. In the former group, the restricted ability of DF1 to secrete both inhibin A and E was restored after luteolysis. Results indicate that dynamic changes in the secretion of both E and inhibin A from the DF contribute to the fall in FSH during the follicular phase and to the generation and termination of the secondary FSH surge, both of which play a key role in follicle selection. In the second study, bFF (two dose levels) was administered to heifers (n = 3-4) for 60 h starting from the time of DF1 emergence. Both doses suppressed FSH (P < 0.05) and blocked DF1 growth to the same extent (P < 0.01), although inhibin A levels were only marginally raised by the lower dose (not significant compared to controls). The high bFF dose raised (P < 0.001) inhibin A to supraphysiological levels ( approximately 1 ng/ml). A large "rebound" rise in FSH occurred within 1 day of stopping both treatments, even though the inhibin A level in the high-dose bFF group was still approximately threefold higher than that in controls. This indicates that desensitization of gonadotropes to inhibin negative feedback is a contributory factor, together with reduced ovarian output of E, in generation of the post-bFF rebound in FSH.     

Menstrual cycle characteristics and predictability of ovulation of Bhutia women in Sikkim, India

Although a woman's menstrual history can have significant implications for health outcomes, few studies have examined menstrual cycle variability in non-western, non-clinically based populations. This study presents menstrual cycle characteristics from Bhutia women living in Gangtok, Sikkim, India. The Bhutia are one of two indigenous populations residing in this small, northeastern state of India. A total of 1067 cycles were recorded by 200 Bhutia women over the course of 12 months. Mean cycle length in this population was similar to reported mean cycle lengths for populations in the U.S (30 days vs. 28 days). Menstrual cycles in this sample were highly variable with most women experiencing more than one short or long menstrual cycle. The frequency of irregular menstrual cycles experienced by individuals also varied significantly by season. A body mass index (BMI) above or below the WHO defined normal range was associated with higher rates of irregular cycles. Leutenizing hormone (LH) and follicle stimulating hormone (FSH) levels were also determined from urine samples collected just before mid-cycle, based on median cycle lengths. Although menstrual cycles in this sample were highly variable, median cycle length was still useful in predicting timing of the pre-ovulatory hormone surges of LH and FSH. Frequency of irregular cycles did impact the successful capture of the LH and FSH peak values.     

Timing of sexual maturity in female rhesus monkeys (Macaca mulatta) housed outdoors

A comparison of the age and season at first parturition was made for spring-born female rhesus monkeys and for females born in the fall to mothers who had been laboratory-housed before being transferred outdoors. Females (N = 9) born during the fall had first parturition during the spring and summer, as did all spring-born females (N = 68), and not during the fall as would be predicted if age were the determining factor. A separate analysis of post-menarchial, spring-born females (N = 5) beginning in September at 29 months of age revealed that the ensuing 12 months were characterized by low serum levels of oestradiol (less than 50 pg/ml), progesterone (less than 1.0 ng/ml), LH (less than 7.0 ng/ml), and FSH (less than 5.50 micrograms/ml). First ovulation subsequently occurred in the fall in all subjects at a mean age of 41.9 +/- 0.1 months, and was preceded by significant elevations in basal LH and FSH, coincident in time with the transition of summer to fall (September). Female copulatory behaviour was restricted to the period surrounding first ovulation, beginning some 2 weeks before and ceasing within 3 days after the oestradiol peak. The most rapid gain in weight occurred during the summer months before first ovulation, and was associated with significant elevations in serum GH and prolactin. These data suggest that season may influence the timing of sexual maturation in rhesus monkeys kept outside in such a way that the occurrence of first ovulation is restricted to the fall and winter months.     

Recombinant luteinizing hormone priming in multiple follicular stimulation for in-vitro fertilization in downregulated patients

Follicle development is controlled amongst other factors by pituitary gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) that act in synergy in completing follicle maturation. Exogenous gonadotropins, combined with gonadotropin-releasing hormone agonists, have been successfully used in patients with ovulatory disorders undergoing assisted reproduction. There is some evidence of a beneficial role of androgens or LH administration before FSH stimulation. This study was designed to verify whether the addition of LH in the early follicular phase, in downregulated patients undergoing follicular stimulation for assisted reproduction, would add benefits in terms of general outcomes and pregnancy rates. We compared two groups of patients one of which was treated with recombinant FSH (rFSH) alone and the other with rFSH plus recombinant LH (rLH), in the early follicular phase only. The number of eggs recovered was higher in the group treated with FSH only; however, the number of embryos available at transfer was similar in the two groups and, more importantly, the number of Grades I and II embryos was higher in the group pretreated with LH. Similarly, although biochemical pregnancy rate and clinical pregnancy rates were similar in both groups, a beneficial role of LH priming was demonstrated by the higher implantation rate achieved in these patients.     

Changes in gonadotrope responsivity to gonadotropin releasing hormone during development of the rhesus monkey

To assess the changing responsiveness of pituitary gonadotropes to gonadotropin releasing hormone (GnRH) during development, 5 male and 5 female rhesus monkeys were studied. Three monkeys of each sex were tested periodically with a subcutaneous injection of 500 micrograms of GnRH dissolved in 50% polyvinylpyrrolidone (PVP) beginning at 2 to 4 weeks of age and continuing into young adulthood. The remaining 4 monkeys received injections of the vehicle (PVP) alone and served as controls. Serum concentrations of bioactive luteinizing hormone (LH) were determined by an interstitial cell testosterone bioassay, and follicle-stimulating hormone (FSH) levels were measured by radioimmunoassay. Baseline FSH levels in the 5 female neonatal monkeys were higher than those of the 5 male neonatal monkeys during the first 2 months of life. In both sexes, FSH concentrations decreased with age, and FSH was barely detectable by 6 months. Baseline LH values in the 5 female monkeys declined during the first 6 months of the study and were undetectable (less than 0.5 micrograms/ml) at 6 months of age. Baseline LH levels in 4 of the 5 neonatal males also declined to undetectable concentrations by 6 months of age. During the first 3 months of life, there was a striking increase in the serum concentrations of both LH and FSH following GnRH. Although the LH responses to GnRH (delta LH) were similar in males and females of comparable ages, the FSH responses (delta FSH) were considerably greater in the female monkeys. In the males, the delta LH exceeded the delta FSH, whereas in the females, the delta FSH were greater than the delta FSH. In both sexes, the delta LH and delta FSH generally were greatest in the youngest monkeys and decreased gradually with increasing age. By 6 months, the gonadotropin responses to GnRH either were undetectable (males) or very small (females). After 6 months there was no longer an increase in serum gonadotropins after GnRH in either sex until 1.5-4 years (females) or 3 years (males) of age. The delta LH in response to GnRH in the male monkeys 3-5 years of age were comparable to the responses during the first month after birth. Serum concentrations of FSH in the adult males, however, did not increase after GnRH. In the female monkeys, serum levels of LH and FSH increased after GnRH at 1.5 years (1 monkey) and 4 years (2 monkeys) of age. The delta LH were similar to those of the 1- to 2-month-old female monkeys. The delta FSH, however, were variable and were approximately 20% of the neonatal response. In these young adult female monkeys the delta LH exceeded the delta FSH.(ABSTRACT TRUNCATED AT 400 WORDS)