Summary. Adult Soay rams were infused for 21 days with 50 μg buserelin/day, using s.c. implanted osmotic mini-pumps. The continuous treatment with this LHRH agonist induced a supraphysiological increase in the blood concentrations of LH (15-fold) and testosterone (5-fold) followed by a decrease below pre-treatment values after 10 days. The blood concentrations of FSH showed only a minimal initial increase but the subsequent decrease was dramatic, occurring within 1 day. By Day 10 of treatment, the blood concentrations of all 3 hormones were low or declining, LH pulses were absent in the serial profiles based on 20-min blood samples and the administration of LHRH antiserum failed to affect the secretion of LH or testosterone. By Day 21, the secretion of FSH, LH and testosterone was maximally suppressed. The i.v. injection of 400 ng LHRH was totally ineffective at stimulating an increase in the blood concentrations of LH while the i.v. injection of 50 μg ovine LH induced a normal increase in the concentrations of testosterone; this confirmed that the chronic treatment with the LHRH agonist had desensitized the pituitary gonadotrophs without markedly affecting the responsiveness of the testicular Leydig cells. The ratio of bioactive:radioimmunoactive LH did not change during the treatment. The long-term effect of the infusion was fully reversible as shown by the increase in the blood concentrations of FSH, LH and testosterone and the return of normal pulsatile fluctuations in LH and testosterone within 7 days of the end of treatment.
G. A. Lincoln, H. M. Fraser, and M. P. Abbott
J. Barrett, D. H. Abbott, and L. M. George
Summary. Pheromonal signals from the dominant female marmoset monkey were implicated in maintaining the suppression of LH secretion and ovulation in socially subordinate females. When subordinate, and reproductively suppressed, female marmoset monkeys were removed from their group without scent contact with their dominant females, subordinate females in control group 1 (N = 8) and control group 2 (N = 5), ovulated 10·8 ± 1·4 days and 10·4 ± 0·8 days respectively (mean ± s.e.m.) after separation. Subordinate females (N = 8) removed from their dominant female and group, but maintained in scent contact only with their dominant females, showed a delay in the onset of ovulation (31·0 ± 6·4 days) compared with control groups 1 and 2. Plasma LH concentrations of subordinate females during the scent transfer phase were lower than in controls without scent transfer and comparable to those seen whilst the females were subordinates in groups. Contact of subordinate females with olfactory stimuli from dominant females therefore maintains the suppression of both LH secretion and ovulation in socially subordinate female marmosets. Such pheromonal cues provide evidence of a quantifiable link between dominant female marmosets and the maintenance of physiological suppression of reproduction in their female subordinates.
Keywords: marmoset; reproductive suppression; pheromones; ovulation; progesterone
S. E. Dodson, M. P. Abbott, and W. Haresign
Summary. To define gonadotrophin secretion rates in the prepubertal heifer, 12 Hereford × Friesian heifers were blood-sampled at 15-min intervals for periods of 24 h every 4 weeks from 3 weeks of age until puberty. Radioimmunoassay of plasma LH concentrations showed that, although LH episode frequency increased with age, overall mean LH concentrations and basal LH concentrations decreased between 3 and 15 weeks of age and then increased to 35 weeks of age. The validity of these trends in relation to biological activity of plasma LH was investigated using an in-vitro Leydig cell bioassay. Samples were selected from 24-h profile bleeds of 4 heifers at 3, 7, 11, 15, 19, 27 and 39 weeks of age. No significant differences were found in the patterns of change in overall mean LH concentrations, basal LH concentrations or LH episode amplitude when comparing the estimates obtained by radioimmunoassay with those by bioassay from birth over the prepubertal period. These results indicate that the changes with age observed by radioimmunoassay are representative of changes in biologically active hormone.
Keywords: bioassay; radioimmunoassay; LH; puberty; heifer
C. G. Faulkes, D. H. Abbott, and J. U. M. Jarvis
Summary. To investigate the endocrine cause of reproductive suppression in non-breeding female naked mole-rats, animals from 35 colonies were studied in captivity. Urinary and plasma progesterone concentrations were elevated in pregnant females (urine: 10·0–148·4 ng/mg Cr, 27 samples from 8 females; plasma: 3·6–30·0 ng/ml, 5 samples from 5 females; Days 21–40 of pregnancy) and cyclic breeding females (urine: 0·5–97·8 ng/mg Cr, 146 samples from 7 females; plasma: < 1·0–35·4 ng/ml, 25 samples from 7 females). The latter group showed cyclic patterns of urinary progesterone, indicating a mean ovarian cycle length of 34·4 ± 1·6 days (mean ± s.e.m.) with a follicular phase of 6·0 ± 0·6 days and a luteal phase of 27·5 ± 1·3 days (19 cycles from 9 breeding females). In non-breeding females urinary and plasma progesterone values were undetectable (urine: < 0·5 ng/mg Cr, 232 samples from 64 females; plasma: < 1·0 ng/ml, 7 samples from 6 females). Breeding females had higher (P < 0·001) plasma LH concentrations (3·0 ± 0·2 mi.u./ml, 73 samples from 24 females) than did non-breeding females (1·6 ± 0·1 mi.u./ml, 57 samples from 44 females). Urinary and plasma progesterone concentrations in non-breeding females from wild colonies situated near Mtito Andei, Kenya, were either below the assay sensitivity limit (urine: < 0·5 ng/mg Cr, 11 females from 2 colonies; plasma: < 1·0 ng/ml, 25 females from 4 colonies), or very low (plasma: 1·6 ± 0·6 ng/ml, 15 females from 4 colonies).
In captivity, non-breeding females removed from their colonies (i.e. the dominant breeding female) and either paired directly with a non-breeding male (N = 2), or removed and housed singly for 6 weeks before pairing with a non-breeding male (N = 5) may develop a perforate vagina for the first time in as little as 7 days. Urinary progesterone concentrations rose above 2·0 ng/mg Cr (indicative of a luteal phase) for the first time 8·0 ± 1·9 days after being separated.
These results suggest that ovulation is suppressed in subordinate non-breeding female naked mole-rats in captive and wild colonies, and show that plasma LH concentrations are significantly lower in these non-breeding females. This reproductive block in non-breeding females is readily reversible if the social factors suppressing reproduction are removed.
Keywords: reproductive suppression; naked mole-rats; ovarian cycles; hystricomorph rodent
C. G. Faulkes, D. H. Abbott, and J. U. M. Jarvis
Summary. To investigate possible anatomical and endocrine differences between breeding and non-breeding male naked mole-rats, 113 animals from 24 captive and 4 wild colonies were studied.
While breeding males had larger reproductive tract masses compared to non-breeders relative to body mass (P < 0·01), spermatogenesis was active in all of the non-breeding males examined histologically (n = 9) and spermatozoa were present in the epididymides. Compared with non-breeders, breeding males had significantly higher urinary testosterone concentrations (mean ± s.e.m.: 23·8 ± 2·3 vs 5·2 ± 1·4 ng/mg Cr respectively; P < 0·001), and plasma LH (10·7 ± 1·7 vs 5·0 ± 0·8 mi.u./ml respectively; P < 0·01). Single doses of 0·1, 0·5 or 1·0 μg GnRH produced a significant rise in plasma LH concentrations 20 min after s.c. injection in breeding and non-breeding males at all doses (P < 0·001). However, there were differences in the magnitude of the LH response following administration of GnRH between breeding and non-breeding males, with non-breeding males showing a dose–response and having lower plasma LH concentrations 20 min after a single injection of 0·1 or 0·5 μg (P < 0·05), but not 1·0 μg, GnRH. This apparent lack of pituitary sensitivity of non-breeding males to single doses of exogenous GnRH was reversed by 4 consecutive injections of 0·5 μg GnRH at hourly intervals, suggesting that the reduced sensitivity may be the result of insufficient priming of the pituitary by endogenous GnRH.
These results indicate that, despite the fact that non-breeding males were apparently producing mature gametes, clear endocrine deficiencies existed in male naked mole-rats.
Keywords: reproductive suppression; naked mole-rats; hystricomorph rodent; testosterone; LH
J. Barrett, D. H. Abbott, and L. M. George
Subordinate female marmoset monkeys remain anovulatory and have low plasma concentrations of luteinizing hormone (LH) when maintained with their dominant females. Olfactory cues from the dominant female have been implicated in maintaining this reproductive suppression. Subordinate females that received either ablation of the vomeronasal organ (an accessory olfactory organ; n = 3), ablation of the main olfactory epithelium (n = 4), or both lesions (n = 5) did not ovulate in the following 7 weeks while housed with their dominant female. Plasma LH concentrations following either or both lesions were similar to pre-lesion concentrations. Olfactory lesions (verified by histological and behavioural trials) did not impair reproductive activity, as olfactory-lesioned dominant females underwent ovarian cycles of similar duration to intact dominant females. Lesioned subordinate females (n = 6), maintained in visual-only contact with their dominant female and group ovulated 29.1 ± 9.3 days (mean ± sem) after physical separation from their dominant females; this first onset of ovulation was significantly delayed (P < 0.05) compared with intact subordinate females completely isolated from their dominant females and group (10.8 ± 1.3 days, n = 8). Behavioural and visual cues together with olfaction all appear to play important roles in maintaining the suppression of ovulation in subordinate female marmoset monkeys.
H. M. Fraser, A. S. McNeilly, M. Abbott, and R. A. Steiner
Summary. A dose of 100 μl of a potent ovine LHRH gamma globulin inhibited ovulation in the cyclic rat when administered at 12:00 h on the day of pro-oestrus. A dose of 10 ml of the preparation was administered i.v. to female stumptailed macaques to achieve circulating antibody titres 3–4-fold higher than in the rat. In an ovariectomized macaque, this caused a marked fall in serum concentrations of LH to less than 10% of pretreatment values and also a significant, though less pronounced, fall in FSH. Six monkeys were treated with the LHRH gamma globulin during the mid—late follicular phase of the cycle. In 2 monkeys in which serum oestradiol concentrations were <100 pg/ml at the time of antibody administration, the rising oestradiol levels were abruptly suppressed and the normal mid-cycle LH surge failed to occur. Serum concentrations of LH and FSH declined to low levels for 8–10 days after which time normal follicular development occurred. In the remaining 4 monkeys in which follicular development was more advanced as indicated by serum oestradiol concentrations of >100 pg/ml, the antibodies induced either a transient decline or had no effect on the rising serum concentration of oestradiol. An LH/FSH surge followed by a rise in serum progesterone occurred in these macaques. When the antibodies were administered to a further 6 macaques, which had also been treated with oestradiol benzoate during the early follicular phase to induce an LH surge, the neutralization of LHRH again failed to block the surge even when the dose of antibody was increased to 20 ml.
The results show that LHRH antibodies were unable to block the LH surge in the macaque. They contrast with results obtained with LHRH immunoneutralization in the sheep, rat, hamster, mouse and bird and suggest that the ability of oestrogen to induce an LH surge by acting directly on the LHRH-primed anterior pituitary gland is more dominant in the primate.
D. H. Abbott, A. S. McNeilly, S. F. Lunn, M. J. Hulme, and F. J. Burden
Summary. Plasma concentrations of progesterone, cortisol, LH and prolactin were measured in dominant and subordinate female marmosets in 10 well-established peer groups. Subordinate females never ovulated, had a reduced LH response to LH-RH and showed no positive feedback LH surge after oestrogen administration. There was no evidence of elevated plasma cortisol levels or hyperprolactinaemia in subordinates and all showed a similar prolactin response to TRH in comparison with dominants. However, subordinates showed a reduced prolactin response to metoclopramide. These results clearly indicate that high circulating levels of cortisol or prolactin are not responsible for the inhibition of ovulation in female marmosets.
J. B. Carroll, D. H. Abbott, L. M. George, J. E. Hindle, and R. D. Martin
Summary. A non-invasive study of urinary hormones in 6 captive female Goeldi's monkeys provided accurate information on reproductive function. Conjugated oestrone accounted for 80–85% of the urinary oestrone and oestradiol measured. Radioimmunoassay measurements of conjugated oestrone provided a reliable indicator of cyclic ovarian function (mean cycle length: 24·1 ± 0·9 days; n = 9) and pregnancy (gestation: 145, 155 days; n = 2). Measurements of urinary progesterone and pregnanediol glucuronide were only reliable as indicators of ovarian cyclicity. Elevations in urinary conjugated oestrone coincided with luteal-phase elevations of urinary progesterone and pregnanediol glucuronide. Urinary LH concentrations provided no indication of pituitary activity. However, the frequencies of female sexual solicitations of males were maximal when oestrone conjugate concentrations rose, suggesting a peri-ovulatory period. Ovulation was suppressed in 1 of 3 subordinate females housed in male–female–female trios.
Keywords: monkey; oestrogen; progesterone; pregnanediol glucuronide, LH; ovarian cycle; pregnancy; urinary hormones
C. G. Faulkes, D. H. Abbott, J. U. M. Jarvis, and F. E. Sherriff
Summary. To investigate possible differential pituitary secretion of LH in breeding and non-breeding female naked mole-rats, the LH responses to administration of exogenous GnRH were measured in 55 females from 20 captive colonies. Single doses of 0·1, 0·5 or 1·0 μg GnRH produced a significant rise in plasma LH concentrations 20 min after s.c. injection in breeding and non-breeding females at all doses (P < 0·001).
While at the highest dose of 1·0 μg there was no difference in the LH response between breeding and non-breeding females, as the dose was lowered there was a progressive decline in the LH response in non-breeding females such that, at the 0·1 μg dose, GnRH produced only a small, but significant, increase in plasma LH (1·3 ± 0·2 to 2·9 ± 0·5 mi.u./ml, N = 5) compared with breeding females (3·4 ± 0·8 to 9·6 ± 2·0 mi.u./ml, N = 6). The LH responses of the latter were not significantly reduced at the lower doses of GnRH.
The apparent lack of sensitivity to low doses of exogenous GnRH in non-breeding females was reversed by 4 consecutive 1-h injections of 0·1 μg, which produced a rise in LH from 1·2 ± 0·2 to 9·0 ± 0·2 mi.u./ml (N = 4), comparable to that of breeding females given a single injection of 0·1 μg GnRH.
These results suggest that the anterior pituitary in non-breeding female naked mole-rats is less sensitive to low doses of exogenous GnRH than in breeding females, possibly due to a lack of priming by endogenous GnRH. Therefore, the socially-induced block to ovulation in non-breeding female naked mole-rats may be due to inhibition of hypothalamic GnRH secretion.
Keywords: naked mole-rat; reproductive suppression; LH; pituitary; GnRH