Absence of brain opioid peptide modulation of luteinizing hormone secretion in the prepubertal gilt

Three experiments were conducted to evaluate the role of endogenous opioid peptides (EOP) in modulating luteinizing hormone (LH) secretion in the prepubertal gilt. In Experiment I, 8 prepubertal (P) gilts, 160-170 days of age (puberty = 197 +/- 10 days), received either 1 (n = 2), 3 (n = 3), or 6 (n = 3) mg/kg BW of naloxone (NAL), an opiate antagonist, in saline i.v. Blood was collected by jugular vein cannula every 15 min for 2 h before and 2 h after NAL. All doses of NAL failed to alter serum LH concentrations. In Experiment II, 21 P gilts 160-170 days of age and 21 mature (M) gilts were ovariectomized (OVX). At the time of OVX, gilts were classified as prepubertal if their ovaries were devoid of corpora albicantia and corpora lutea. Three weeks after OVX, P and M gilts were injected twice daily for 10 days with either 0.85 mg/kg BW of progesterone (P4) or oil vehicle (V), resulting in the following groups: PP4 (n = 11), PV (n = 10), MP4 (n = 11), and MV (n = 10). All gilts received 1 mg/kg BW of NAL on the last day of treatment. Blood samples were collected via a jugular cannula every 15 min for 4 h before and 2 h after NAL treatment. NAL treatment resulted in an increase (p less than 0.05) in serum LH concentrations only in the MP4 gilts. In Experiment III, 15 OVX gilts 280 days of age were used. Ten of the 15 gilts were OVX prior to puberty at 160 days of age and were classified as chronologically mature (CM) at the time of treatment. The remaining 5 gilts were OVX after puberty, and were classified as sexually mature (SM) at the time of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Opiate antagonist treatment reinstates estrous cycles in middle-aged persistent-estrous rats

Middle-aged female rats display luteinizing hormone (LH) surge deficits and cycle irregularity followed by the onset of persistent estrus (PE). The central nervous system has been identified as a primary locus of failure in PE rats, but the particular neural elements involved have not been determined. The goal of the present study was to identify a role for endogenous opioid peptides (EOP) in age-related acyclicity by evaluating the effect of opiate antagonist treatment on vaginal cytology in PE rats. PE rats were administered, s.c., saline (SAL), naloxone (NAL) or naltrexone (NTX) once daily for 20 days, or repetitively on Day 1 and on successive proestrus days if cyclicity was resumed. Single NTX (50 mg/kg), but not NAL (2 mg/kg), treatment interrupted the PE state in almost half of treated animals. Daily or repetitive proestrus NTX (10 mg/kg) treatment interrupted PE more frequently, and many animals displayed repeated estrous cycles and ovulation. Afternoon LH surges were observed after initial NTX treatment in animals displaying PE interruption. This demonstration that LH surges and ovulatory cycles can be reinitiated in PE rats with NTX suggests that dysfunction in the 'brake' on EOP secretion during proestrus may be one of the neuroendocrine impairments mediating acyclicity in aging female rats.     

A suppression of gonadotropin secretion by cortisol in castrated male rhesus monkeys (Macaca mulatta) mediated by the interruption of hypothalamic gonadotropin-releasing hormone release

Four orchidectomized rhesus monkeys (3-3.5 yr of age) were treated for 62 days with daily i.m. injections of hydrocortisone acetate (HCA) at a dose of 10-20 mg/(kg BW X day), and blood samples were obtained daily or every other day before, during, and after treatment. Hydrocortisone acetate injections resulted in a progressive rise in mean plasma cortisol from basal concentrations of 17-35 micrograms/100 ml prior to initiation of steroid treatment to approximately 150 micrograms/100 ml 5 wk later. When serum cortisol concentrations reached 100 micrograms/100 ml, 3-4 wk after the initiation of HCA treatment, circulating luteinizing hormone (LH) and follicle-stimulating hormone (FSH) began to decline, reaching nondetectable concentrations 35 days later. Withdrawal of HCA resulted in a return in plasma cortisol concentrations to pretreatment control levels, which was associated with a complete restoration of gonadotropin secretion. In 2 animals, administration of an intermittent i.v. infusion of gonadotropin-releasing hormone (GnRH) (0.1 micrograms/min for 3 min once every hour), which appears to stimulate the gonadotropes in a physiologic manner, reversed the cortisol-induced inhibition of gonadotropin secretion, restoring circulating LH and FSH concentrations to within 80-100% of control. These results suggest that, in the rhesus monkey, the major site of the inhibitory action of cortisol on gonadotropin release resides at a suprapituitary level and is mediated by interruption of hypothalamic GnRH release.     

Influence of endogenous opiates on anterior pituitary function

In general, the endogenous opioid peptides (EOP), morphine (MOR), and related drugs exert similar effects on acute release of pituitary hormones. Thus administration of opiates produces a rapid increase in release of prolactin (PRL), growth hormone (GH), adrenocorticotropin (ACTH), and antidiuretic hormone (ADH), and a decrease in release of gonadotropins and thyrotropin (TSH). Although not yet fully established, there is growing evidence that the EOP participate in the physiological regulation of pituitary hormone secretion. Thus naloxone (NAL), a specific opiate antagonist, has been shown to reduce basal serum levels of PRL and GH, and to elevate serum levels of LH and follicle stimulating hormone in male rats. Other reports have shown that NAL can inhibit the stress-induced rise in serum PRL, raise the castration-induced increase in serum LH to greater than normal castrate values, and counteract the inhibitory effects of estrogen and testosterone on LH secretion. Opiates appear to have no direct action on the pituitary, but there is evidence that they can alter activity of hypothalamic dopamine and serotonin in modulating secretion of pituitary hormones.     

Delayed puberty in lambs chronically treated with oestradiol

Intact female lambs were chronically treated with low levels of oestradiol by Silastic implant from 20 weeks of age. Reproductive cycles were initiated in only 33% of these lambs (3 of 9) compared to 80% of untreated females (11 of 14) by 45 weeks when the study was terminated. Moreover, in the 3 oestradiol-treated lambs which began cycles, the age at first oestrus was delayed 3 weeks (37 +/- 1 weeks of age vs 34 +/- 1 weeks of age for untreated controls). Retardation of the pubertal process was not due to absence of the pubertal rise in circulating LH. At about 32 weeks of age, chronic oestradiol treatment was no longer able to suppress tonic LH secretion and serum LH increased in intact, oestradiol-treated lambs. These results indicate that a maturational decrease in responsiveness to oestradiol inhibition of tonic LH secretion can be demonstrated in the intact female, as in the ovariectomized female. However, chronic oestradiol suppression of prepubertal LH secretion also delays onset of reproductive cycles. This finding raises the possibility that low tonic LH secretion, presumably in the form of slow pulses, is necessary for development or maintenance of ovarian function before puberty. In the absence of LH during the last part of sexual maturation, the ability of the ovary to respond to the high frequency LH pulses during the pubertal gonadotrophin rise may be delayed.     

Development of opiate ([3H] naloxone)-binding sites in female rabbit brain: correlation with prepubertal gonadotropin secretion

In neurochemical terms, little is known concerning the control of puberty onset in the female rabbit. In view of the established involvement of brain opiates in the sexual maturation of the rat, we have investigated the prepubertal development of opiate-binding sites in the hypothalamus and cerebral cortex of the rabbit. Binding of the opiate antagonist, [3H] naloxone, to thick (350 micron) slices of rabbit brain was found to be reversible, stereospecific, saturable, and of high affinity. In all respects these sites possessed the characteristics of opiate receptors. Specific binding (Bmax and KD) values were determined at 1, 8, 29, 40, 51, 100, and 168 days after birth in the hypothalamus and cerebral cortex. All all ages binding in the hypothalamus was higher, per mg of tissue, than in the cortex. Major differences in the pattern of development were also evident. In the cortex the Bmax slowly increased from a minimum at Day 1 to a maximum at about 100 days when puberty normally occurs. In contrast, binding in the hypothalamus rose rapidly to a maximum at 40 days and then fell abruptly, by about 40% at Day 51, after which a slow increase through puberty took place. This peak in the hypothalamic Bmax value correlates closely with the major prepubertal surge of gonadotropin secretion. It remains to be determined whether the coincidence of spontaneous gonadotropin secretion with the rapid appearance of hypothalamic opiate receptors is developmentally meaningful for the reproductive system.     

Daily rhythms of serum luteinizing hormone in the immature hamster are estradiol-dependent

In the female Syrian hamster (Mesocricetus auratus), daily rhythms of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) begin several weeks before regular vaginal estrous cycles are initiated. These rhythms, which appear rather abruptly at about 16 days of age, are dependent on the presence of the ovaries. The experiments described here were intended to determine the nature of the ovarian information required for the initiation and maintenance of the daily LH surge. This surge characterizes the daily cycle of LH and occurs each afternoon at about 1700 h in the intact animal between 2 and 5 weeks of age. Females were ovariectomized at 14 or 15 days of age and implanted with constant-release Silastic capsules of estradiol (E) or progesterone (P). Blood samples were collected at 21 days of age at 1400 or 1700 b, and the serum was assayed for LH, P, and E. While ovariectomy abolished the afternoon surge of serum LH that was observed in sham-operated controls, implantation of E effectively replaced the ovaries. Implantation of P was without effect on LH levels; when P plus E was implanted, the effect was similar to that of E alone. These results suggest that ovaries of the 2-week-old hamster secrete estrogen necessary for the initiation of cyclical LH release.     

Direct action of opioid peptides and naloxone on gonadotropin secretion by cultured rat anterior pituitary cells

Most current evidence indicates that opiates act via the hypothalamus to influence pituitary function. There are no detailed studies concerning pituitary site of action. Direct action of opioids on gonadotropin secretion was studied using enzymatically dispersed rat pituitary cells maintained in a monolayer culture. A time course study demonstrated that pretreatment with beta h-endorphin (beta h-End) (10(-7) M) initiated an inhibitory effect on LH release at 24 h, and was more evident at 48 h. A dose dependent decrease in LH release by beta h-End in concentrations of 10(-9) M to 10(-7) M was shown, whereas FSH was unchanged. Equimolar concentrations (10(-7)M ) of methionine enkephaline (Met-Enk) and D-ala2-met-enkephalinamide (DALA) produced a significant decrease in LH. Naloxone (NAL) (10(-5)) enhanced the release of both LH and FSH, and also blocked the inhibitory effect of beta h-End on LH release. These results indicated that opioid peptides act directly on anterior pituitary cells, decreasing the release of LH, but not of FSH. NAL also had a direct effect increasing the release of LH and FSH, and blocking the inhibitory action of beta h-End.     

Daily rhythms of luteinizing hormone and follicle-stimulating hormone persist in female hamsters sterilized by neonatal administration of monosodium glutamate

Monosodium glutamate (MSG) was used to evaluate the importance of the arcuate nucleus of the hypothalamus in the expression of daily gonadotropin rhythms in female golden hamsters. These daily rhythms of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which also occur in prepubertal females, are characterized by afternoon surges. Neonatal administration of MSG induces degeneration of perikarya in the arcuate nucleus and renders females permanently anovulatory. MSG was injected at 8 days of age; at 21 days, the animals were weaned and sorted by sex into groups of 5-7. Blood samples were obtained at 1300 and 1700 h at 25, 30, 35, 40, 50, 62, and 192 days of age from MSG-sterilized animals. Saline-injected controls were bled at 25 days and after estrous cycles had been initiated (29-37 days of age). In both control and MSG-injected groups, there was an afternoon surge of LH and FSH at 25 days of age. These daily surges persisted in MSG-injected animals. The ovaries of these animals were characterized by an abundant interstitium and arrested follicular development. Progesterone levels of MSG-anovulatory animals also reflected the rhythmicity of LH and FSH, with a significant increase occurring between 1300 and 1700 h. Thus, MSG did not affect the daily circadian-based rhythmicity in gonadotropin secretion even though adult-age animals were infertile. These results suggest that perikarya of the arcuate nucleus affected by MSG are not required for generation of daily LH and FSH rhythms.     

Endogenous opiate involvement in acute and chronic stress-induced changes in plasma LH concentrations in the male rat

The present study was carried out to examine the possible role of the endogenous opioid peptides ( EOP 's) on the pituitary luteinizing hormone (LH) response to both acute and chronic stress and to food deprivation. Thirty minutes after acute (2 min.) exposure to ether, plasma LH levels were elevated compared to controls; morphine (MOR) treatment prior to stress prevented this response. More prolonged etherization (15 minutes) significantly depressed circulating LH, whereas naltrexone ( NALT ), a specific opiate antagonist, reversed this decline. Immobilization for 8 hours resulted in a significant initial increase in LH release, followed by a decline toward baseline levels. Naltrexone treatment increased the magnitude of the acute LH rise, and attenuated the subsequent decrease in plasma LH. The effect of chronic stress on circulating LH was also examined. Plasma LH levels were depressed for 3 consecutive days following subcutaneous gauze pad implantation, whereas 3 daily NALT injections returned LH to control levels. Complete food deprivation for 5 days also resulted in a significant decline in circulating LH. Injection of NALT 3 times daily reversed this decline on days 2, 3 and 4 of treatment. These results support the hypothesis of a mediatory role for the EOP 's in the effect of both chronic stress and food deprivation on LH release in the rat.     

Naloxone enhances LH but not FSH release during various phases of the estrous cycle in the ewe

Suffolk x whiteface ewes were infused with 0.5 mg/kg/hr naloxone hydrochloride (NAL) for 6 hrs during the early, mid and late luteal and early follicular phases of the estrous cycle. Basal serum luteinizing hormone (LH) concentration was increased by NAL during each trial in the luteal phase and LH pulse amplitude was proportionately increased by 158%, 164% and 350% during the early luteal, mid luteal and early follicular phases, respectively. The apparent NAL induced increase (92%) in LH pulse amplitude during the late luteal phase was not significant. NAL only affected LH pulse frequency during the early follicular phase, when it was decreased. Mean serum follicle stimulating hormone (FSH) concentration was not affected by NAL. The results of this study indicate that endogenous opioid peptides (EOPs) may partially mediate the suppressive influence of estradiol-17 beta (E2) on LH pulse amplitude and also the stimulatory effect of E2 on LH pulse frequency in the early follicular phase. The data may suggest that NAL enhances the amplitude of pulses of gonadotropin releasing hormone (GnRH) by counteracting E2 inhibitory effects on LH release at the level of the pituitary. Alternately, some component of E2 feedback may be an EOP mediated component at the level of the hypothalamus.     

Estradiol regulation of luteinizing hormone secretion in heifers of two breed types that reach puberty at different ages

The working hypothesis was that 17 beta-estradiol (E(2)) negative feedback on the hypothalamic-pituitary axis in regulation of LH secretion decreases during peripuberty in heifers of 2 different genotypes. We investigated whether Bos indicus heifers had a period postpuberty, as compared with prepuberty, of greater E(2) inhibition of LH secretion at a time when heifers of this genotype have been reported to have a period of anestrus. Prepubertal heifers 9 mo of age of 2 genotypes (B. indicus and B. taurus) were assigned to 3 groups (6 animals/group) to either remain intact (control), be ovariectomized, or be ovariectomized and implanted with E(2). Variables evaluated from 10 to 28 mo of age were circulating concentrations of progesterone (P(4)), presence of corpora lutea, and pulsatile pattern of LH release. Results confirmed that B. taurus heifers attained puberty at younger ages (P < 0.001) and at lower live weights (P = 0.015) than did B. indicus heifers (507 +/- 37 days of age vs. 678 +/- 7 days of age; 259 +/- 14 kg vs. 312 +/- 11 kg; respectively). There was cessation of E(2) inhibition of LH pulses coincident with the onset of puberty in heifers of both breed types but at a much younger age in B. taurus heifers. There was no evidence of enhanced negative feedback of E(2) on LH secretion subsequent to puberty in B. indicus heifers nor was there cessation of estrous cycles in control heifers of either breed type after puberty.     

Glutamate: A major neuroendocrine excitatory signal mediating steroid effects on gonadotropin secretion

The preovulatory gonadotropin surge is induced by progesterone in the cycling female rat or in the ovariectomized estrogen-treated female rat after adequate estrogen-priming activity is present. The source of progesterone under physiological conditions could be the ovary and/or the adrenal. Since the GnRH neuron does not possess estrogen and progesterone receptors, its function is modulated by other CNS neurotransmitters and neurosecretory products. Among these, excitatory amino acids (EAAs) have now been shown to play an important role in the regulation of pulsatile gonadotropin release, induction of puberty and preovulatory and steroid-induced gonadotropin surges. Glutamate, the major endogenous EAA exerts its action through ionotropic and metabotropic receptors. The ionotropic receptors consist of two major classes, the NMDA (N-methyl-D-aspartate) and non-NMDA: kainate and AMPA ( --amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors. EAA receptors are found in hypothalamic areas involved with reproduction. While both NMDA and non-NMDA receptors are involved in the regulation of LH secretion, the NMDA receptors appear to be involved with the regulation of puberty and FSH secretion as well. Steroids increase the release rates of glutamate and aspartate in the preoptic area during the gonadotropin surge. Steroids may also regulate the hypothalamic AMPA receptors.     

A possible dual mechanism involved in the inhibitory influence of suckling on luteinizing hormone release in the ovariectomized rat.

A study was conducted to further understand involvement of the endogenous opioid peptides in suckling-induced inhibition of LH release in ovariectomized rats. The first experiment was designed to determine the effect of an opioid antagonist, naloxone (NAL, 1.0 mg. kg-1h-1), on the increase in peripheral LH concentration 18 h after pup removal and on the decrease in LH concentration 18 h after pup return. Infusion of NAL during the 18 h after pup removal or during the 18 h after pup return neither accentuated nor attenuated serum LH concentrations. The second experiment was designed to determine the effect of NAL on peripheral LH concentrations in continuously suckled rats. Serum LH increased (p less than 0.10 and p less than 0.005, respectively) in response to 18 and 36 h of NAL infusion. The third experiment was designed to determine the effect of pup removal during NAL infusion on serum LH. Peripheral LH concentrations were not different in the rats treated with 36 h of NAL infusion whether they were suckled for the duration of the infusion or nonsuckled for the last 18 h of infusion. These results suggest that suckling may inhibit LH release through two mechanisms. The first may be an opioid-independent or enhanced opioid tone mechanism important for the initiation of the inhibitory effect of suckling on LH release, while the second may be an opioid-dependent mechanism important for the sustained inhibitory effect of suckling on LH release.     

Treating heifers with GnRH from 4 to 8 weeks of age advanced growth and the age at puberty

In heifer calves, an early transient increase in circulating concentrations of LH is associated with early follicular development and is thought to regulate the timing of puberty. In an attempt to hasten the onset of sexual maturity, the early rise in LH concentration was advanced by injecting heifer calves with 120 ng/kg of GnRH (n=6) twice daily from 4 to 8 weeks of age; control calves received saline (n=6). Blood samples were collected every 15 min for 10h at 4, 8, 14, 20, 26, 32, 38, 44 and 50 weeks of age. Treatment with GnRH increased mean circulating concentrations of LH at 8 weeks of age (P<0.05), LH pulse frequency at 4 and 8 weeks of age (P<0.05), and reduced the mean age at puberty by 6 weeks (56.8+/-1.7 versus 62.8+/-2.4 weeks of age, for GnRH treated and control calves, respectively; P=0.04). Body weight gain was greater in GnRH-treated calves than control calves (P<0.05), and the rate of weight gain was shown to be a significant covariate within age at puberty. In conclusion, we suggest that the timing of the early rise in LH concentrations is a critical signal involved in the timing of puberty in heifers.     

The effects of melatonin and hypothyroidism on estradiol and gonadotropin levels in female Syrian hamsters

Since melatonin injections administered near the end of the daily photoperiod influence both gonadal and thyroid hormones in the female hamster, the present study was designed to compare the effects of melatonin and hypothyroidism on the reproductive system and to determine whether thyroid status influenced the action of melatonin on the regulation of the hormones of reproduction. The effects of daily melatonin injections were determined in control hamsters, in hamsters rendered hypothyroid with thiourea, and in hypothyroid hamsters receiving thyroxin (T4) hormone replacement. As previously reported, melatonin injections disrupted estrous cyclicity, disrupted the normal pattern of gonadotropin secretion, and resulted in atrophy of the uterus and vagina. These changes coincided with depressed serum and pituitary prolactin (PRL), and depressed levels of estradiol. The effects of melatonin on uterus, vagina, ovary, and on gonadotropin levels were not prevented by T4 replacement, with the exception of a melatonin-induced increase in serum follicle-stimulating hormone (FSH). This suggested that the cessation of estrous cyclicity was not primarily a result of thyroid deficiency. Hypothyroidism, however, like melatonin, resulted in a reduced number of developing and mature follicles and corpora lutea in the ovaries, and in reduced uterine weight. It also produced follicular atresia, reduced the circulating levels of estradiol, and resulted in reduced incidence of estrus smears. T4 replacement, for 2 weeks, prevented the decline in mature follicles and corpora lutea, reduced the extent of follicular atresia, increased circulating levels of estradiol, and increased uterine weight. PRL and luteinizing hormone (LH) data also provided evidence for antagonistic effects of melatonin and T4 in female hamsters. These data raise the question whether melatonin-induced changes in circulating levels of T4 play a role in the seasonal cycles of reproductive competence in the female hamster.     

Effects of ovariectomy on clock-timed daily gonadotropin rhythms in prepubertal golden hamsters

Daily rhythms of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are measurable in the serum of prepubertal female golden hamsters by 17 days after birth. These rhythms, which are characterized by peak levels at 1700 h, persist until they are replaced by a 4-day rhythm as ovulatory cycles begin, approximately 3 wk later. We have tested the proposition that the ovaries are required for the onset and maintenance of clock-timed gonadotropin release by removing the ovaries and measuring the levels of LH and FSH in prepubertal hamsters. Ovariectomy was performed both before and after the onset of the rhythm and the effect of removal was determined by subsequent collection of blood samples during the mid- to late-prepubertal period. Ovariectomy on 7, 10 or 13 days after birth results in tonic levels of LH and FSH in blood samples collected at 1400, 1700 and 2000 h on Days 17 through 29. Sham-operated or intact controls had significantly elevated levels of these hormones at 1700 h. Ovariectomy on Day 21 and killing on Day 25 at the same times of day abolished the rhythm of serum LH measured in sham-ovariectomized controls. Ovariectomy on Day 21 and killing on Days 26, 28 or 30 at hourly intervals resulted in variable but nonrhythmic patterns of circulating LH. Thus, ovariectomy before the initiation of clock-timed gonadotropin release prevented its initiation; ovariectomy after its initiation abolished the rhythm. These results show that the ovary provides an essential "message" to the brain-pituitary axis for the initiation and maintenance of clock-timed gonadotropin release in prepubertal females.     

Hypothalamic excitatory amino acid system during sexual maturation in female rats

The present results indicate that during sexual maturation the APOA-MBH from rats of 30 days of age released significantly higher quantities of GnRH than the tissue from 16-day-old rats (P < 0.01). The addition of NMDA, an agonist of the excitatory amino acids system (EAAs), to the medium after 30 min of incubation significantly increased (P < 0.01) the GnRH release in normal rats of both ages and this increase was significantly (P < 0.01) higher in 30-day-old rats (to 661%) than in rats of 16 days of age (to 273%). The administration of estrogen-progesterone (EP) to rats of 16 days of age did not modify the GnRH release response to NMDA. On the contrary, at 30 days of age EP administration significantly potentiated the GnRH release response to NMDA since while in the control group NMDA increased the GnRH release to 630%, in the EP-pretreated group this was to around 4700% (P < 0.01). EP pretreatment of prepubertal rats decreases the hypothalamic release of aspartate and glutamate, the excitatory amino acids involved in NMDA neurotransmission and glycine but increases EAAs release in peripubertal rats. On the basis of these results it is proposed that the increase in EAAs release by the hypothalamus is directly connected with the onset of puberty and that the maturation of the positive feedback effect of ovarian hormones on gonadotropin secretion is related to the maturation of the capacity of EP to increase hypothalamic EAAs. Before this maturational event EP inhibits EAAs release as well as gonadotropin release (prepubertal rats). NMDA receptor stimulation leads to a positive mechanism which increases the release of Asp and Glu from APOA-MBH both in prepubertal and peripubertal rats, but EP potentiates this mechanism only in peripubertal rats. This could be an additional neuroendocrine mechanism involved in the increase of gonadotropin during sexual maturation which induces the onset of puberty and the preovulatory discharge of these pituitary hormones.     

Selective release of follicle-stimulating hormone and luteinizing hormone by 5 alpha-dihydroprogesterone and 3 alpha, 5 alpha-tetrahydroprogesterone in pregnant mare's serum gonadotropin-primed immature rats exposed to constant light

The effects of 5 alpha-dihydroprogesterone (5 alpha-DHP) and 3 alpha, 5 alpha-tetrahydroprogesterone (3 alpha, 5 alpha-THP) on follicle-stimulating hormone (FSH) and luteinizing hormone (LH) release were examined in the pregnant mare's serum gonadotropin (PMSG)-primed immature female rat (8 IU PMSG at 28 days of age) maintained in constant light. Control rats kept in 14L:10D conditions exhibited proestrous-like surges of LH and FSH release with peak levels attained at 1800 h on the second day after PMSG treatment. In rats exposed to constant light, the PMSG-induced surges of LH and FSH were not only delayed until 1000 h on the third day after PMSG, resulting in a delay in ovulation, but were also significantly attenuated when compared to the gonadotropin surges that occurred on Day 2 in rats kept under normal light-dark conditions. The administration of 5 alpha-DHP significantly enhanced the release of FSH at 1000 h on Day 3 when compared to constant light-exposed controls, but had no effect on LH. Treatment with 3 alpha, 5 alpha-THP selectively potentiated the release of LH at 1000 h on Day 3 and had an attenuating effect on FSH release on Days 2 and 3. These observations confirm earlier findings in the immature ovariectomized estrogen-primed rat and suggest that 5 alpha-DHP and 3 alpha, 5 alpha-THP may have significant roles in the regulation of FSH and LH secretion.     

A 'window of time' during which testosterone determines the opiatergic control of LH release in the adult male rat

Male rats castrated before puberty (when 26 days of age) showed a progressively decreasing susceptibility to the inhibitory effects of morphine (5 mg/kg) upon LH secretion for up to 28 days after gonadectomy (approximately 100%, 40% and 10% inhibition at 5, 12 and 28 days after castration), but thereafter morphine again caused approximately 50% reduction in serum LH values; the minimum inhibition found at 28 days after castration (age 54 days) occurred at the time at which male rats normally reach puberty. When rats were castrated at 59 days of age, morphine maximally suppressed serum LH concentrations (to less than 70%) 2 and 5 days after castration, but had no effect thereafter. In prepubertal castrates, testosterone replacement between Days 26 and 50 of life resulted in responses to morphine similar to those found in rats castrated after puberty, i.e. serum LH levels were not reduced. Morphine significantly reduced LH levels in prepubertal castrates given testosterone after 60 days of age. Treatment with morphine consistently elevated serum prolactin concentrations (greater than 100%) in castrated rats of all ages, regardless of the time elapsed after gonadectomy. These results indicate a transient fall in the inhibitory opioidergic tone upon LH secretion as the normal age of puberty approaches, that the ability of opiates to alter LH release in adulthood may depend upon testicular steroids secreted during the peripubertal period, and that the LH responses do not reflect general changes in the neuroendocrine response to opiates after castration since the prolactin response to morphine remains intact in rats castrated before and after puberty.