Evidence that oestrogen exerts an equivalent negative feedback action on LH secretion in male and female ferrets

Gonadally intact male ferrets in breeding condition, which received an aromatase inhibitor, 1,4,6-androstatriene-3,17-dione (ATD) s.c. in Silastic capsules, had significantly more LH pulses and higher mean LH concentrations in plasma than did control males implanted with empty capsules. Aromatase activity in the hypothalamus + preoptic area and temporal lobe was strongly suppressed by ATD treatment whereas circulating concentrations of testosterone and oestradiol were not affected. These results suggest that oestradiol, formed via neural aromatization of circulating testosterone, contributes to the feedback regulation of LH secretion in breeding male ferrets just as oestradiol of ovarian origin controls LH secretion in females. No sex difference was observed in the rate at which mean plasma LH concentrations rose after the removal from gonadectomized ferrets of s.c. Silastic capsules containing oestradiol. Daily s.c. injections of oestradiol in oil caused an equivalent, dose-dependent inhibition of LH pulse frequency and mean LH concentrations in plasma of male and female ferrets. These findings suggest that the negative feedback control of pulsatile LH secretion by oestrogen is not sexually differentiated in this reflexly ovulating species. The ferret appears to differ from spontaneously ovulating mammalian species in which the female is generally more sensitive than the male to the inhibitory feedback action of oestradiol on LH secretion.     

Luteinizing and ovulatory action of oestradiol in the pregnant rat

Oestradiol injection on Day 10 of pregnancy in rats, resulted in either ovulation or luteinization in 50% of cases on Day 12. Cytological data showed that the number of pituitary LH cells decreased significantly on Day 11 in all oestradiol-treated animals whether responsive or not to oestrogen by ovarian modifications, while the number of pituitary FSH cells only decreased significantly in females with characteristic ovarian signs of preovulation. Bioassay of pituitary FSH confirmed the cytological data. It is concluded that ovulation and luteinization only occurred in the pregnant rat when oestradiol triggered off a synchronous release of LH and FSH.     

On the evocability of a positive oestrogen feedback action on LH secretion in female and male rats.

Following a single injection of oestradiol benzoate (15 mug/100 g body weight) postpubertally castrated and oestrogen-primed female rats showed a distinct surge of LH secretion, while castrated and androgen-primed females displayed a diminished and delayed surge of LH secretion. On the other hand, postpubertally castrated and oestrogen-primed male rats exhibited only a slight, but significant surge of LH secretion, whereas castrated and androgen-primed males did not display any surge of LH secretion following oestrogen injection. In view of these findings the evocability of a positive oestrogen feedback action on LH secretion is dependent on the sex hormone level during the critical hypothalamic differentiation phase and the functional (priming) phase as well.     

Altered sexual development in male rats after oestrogen administration during the neonatal period.

Male rats given 250 mug oestradiol benzoate by subcutaneous injection on Day 4 of postnatal life showed a marked delay in the onset of the pubertal increase in the weight of the testes and seminal vesicles and in spermatogenesis but not a complete failure of sexual development. The increase in plasma testosterone concentration at puberty was also delayed in oestrogen-treated males but the eventual increase in seminal vesicle weight was closely related in time to the delayed increase in plasma testosterone concentration. Both plasma LH and FSH concentrations were reduced for about 10 days after oestrogen administration as compared to control values. After 22 days of age, plasma LH concentration did not differ significantly from the control values. The plasma FSH concentration of the oestrogen-treated males showed a delayed rise to values equal to or higher than those of controls of the same age. The delayed rise in plasma FSH concentration in the oestrogen treated males preceded the delayed rise in plasma testosterone in these animals. The decrease in plasma FSH concentration from the high prepubertal values to the lower values in adults occurred at different ages in the control and in oestrogen-treated rats but in both groups the decrease occurred as plasma testosterone levels were increasing and the first wave of spermatogenesis was reaching completion. The increase in plasma FSH concentration after castration was reduced in oestrogen-treated males during the period throughout which FSH levels in the intact animals were subnormal but the levels in oestrogen-treated males castrated after the delayed rise in FSH had occurred did not differ from control values. It is suggested that the delayed sexual maturation of male rats treated with high doses of oestrogen in the neonatal period is related principally to abnormalities in the secretion of FSH.     

Increased uterine uptake and nuclear retention of [3H]oestradiol through the oestrous cycle and enhanced end-organ sensitivity to oestrogen stimulation in vitamin B6 deficient rats

Vitamin B6 deficient female rats showed a significantly earlier, greater and more prolonged uptake of a tracer dose of [3H]oestradiol into the uterus, with increased nuclear accumulation, compared with vitamin B6 supplemented animals. This was most marked at oestrus, with little difference at anoestrus. The responses to low doses of ethynyl-oestradiol were greater in ovariectomized deficient animals than in those receiving the supplemented diet, with an increased uterotrophic response and greater induction of peroxidase. In the deficient animals there was virtually complete suppression of LH secretion at doses of ethynyl-oestradiol that had no effect in controls. At high doses of ethynyl-oestradiol there was no difference between the two groups of animals. The results suggest that increased uterine uptake and accumulation of [3H]oestradiol in vitamin B6 deficiency is associated with enhanced end-organ responsiveness to sub-maximal oestrogen stimulation, and that pyridoxal phosphate may have a coenzyme role in oestrogen action.     

Studies on the time and localization of the puberal desensitization to oestrogen in female rats

Immature and postpuberal female rats were ovariectomized at 20 or 27 days of age or on the day of the first vaginal oestrus and chronically implanted with oestradiol benzoate (OB) and cholesterol at the ratios of 1 : 60, 1 : 120 or 1 : 240 on the day following castration. Autopsy was performed on day 6 after implantation and the plasma LH concentration determined by radioimmunoassay. Whereas 1 : 60 and 1 : 120 implants of OB and cholesterol placed into the hypothalamic ventromedial-arcuate region depressed the castration-induced elevation of the LH level before and after puberty, the 1 : 240 mixture was effective only in immature rats, but not after vaginal opening and the first ovulation had occurred. A similar trend was recorded after implantation of OB into the cortical amygdaloid nucleus (CAN). However, the oestrogen dose had to be doubled to get comparable results. Bilateral lesioning of the CAN or deefferentation of the mediocortical amygdala by transection of the stria terminalis did not distinctively influence the LH-suppressing effect of daily s.c. injections of 0.1 or 0.05 microgram OB/100 g b. w. in prepuberal rats. The findings demonstrate a sudden change in the hypothalamic threshold to the gonadotrophin-inhibiting effect of oestrogen over a narrow range of time near the onset of puberty. They furthermore suggest that the mediocortical amygdala is not involved in possible extra-hypothalamic control of the puberal desensitization process.     

Effect of gonadal steroids and gamma-aminobutyric acid on LH release and dopamine expression and activity in the zona incerta in rats

A dopaminergic system in the zona incerta stimulates LH release and may mediate the positive feedback effects of the gonadal steroids on LH release. In this study the mechanisms by which steroids might increase dopamine activity in the zona incerta were investigated. In addition, experiments were conducted to determine whether the inhibitory effects of gamma-aminobutyric acid (GABA) on LH release in the zona incerta are due to suppression of dopamine activity in this area or conversely whether the stimulatory effects of dopamine on LH release are due to suppression of a tonic inhibitory GABAergic system. Ovariectomized rats were treated s.c. with oil, 5 micrograms oestradiol benzoate or 5 micrograms oestradiol benzoate followed 48 h later by 0.5 mg progesterone, and killed 54 h after the oestradiol benzoate injection. At this time the LH concentrations were suppressed in the oestradiol benzoate group and increased in the group treated with oestradiol benzoate and progesterone. The ratio of tyrosine hydroxylase:beta-actin mRNA in the zona incerta was significantly increased by the oestradiol benzoate treatment, but the addition of progesterone resulted in values similar to those in the control group. At the same time, the progesterone treatment increased tyrosine hydroxylase activity in the zona incerta as indicated by an increase in L-dihydroxyphenylalanine (L-DOPA) accumulation after 100 mg 3-hydroxybenzylhydrazine hydrochloric acid (NSD1015) kg-1 and an increase in dopamine release as indicated by a increase in dihydroxyphenylacetic acid (DOPAC) concentrations (one of the major metabolites of dopamine). Ovariectomized rats treated with oestradiol benzoate plus progesterone were also injected i.p. with 75 mg gamma-acetylenic GABA kg-1 (a GABA transaminase inhibitor) to increase GABA concentrations in the brain. This treatment had no effect on the ratio of tyrosine hydroxylase:beta-actin mRNA but decreased L-DOPA accumulation and DOPAC concentrations in the zona incerta, indicating a post-translational inhibition of dopamine synthesis and release. Treatment of ovariectomized rats with oestradiol benzoate followed by 100 mg L-DOPA i.p. to increase dopamine concentrations in the whole brain had no effect on glutamic acid decarboxylase mRNA expression in the zona incerta, although it increased the glutamic acid decarboxylase:beta-actin mRNA ratio in other hypothalamic areas (that is, the medical preoptic area, ventromedial nucleus and arcuate nucleus). In conclusion, the steroids act to increase dopamine activity in different ways: oestrogen increases tyrosine hydroxylase mRNA expression and progesterone acts after translation to increase tyrosine hydroxylase activity and dopamine release (as indicated by increases in DOPAC concentrations). This latter effect may be due to progesterone removing a tonic GABAergic inhibition from the dopaminergic system.     

Seasonal and hormonal control of pulsatile LH secretion in the dairy goat (Capra hircus)

In Exp. 1, the changes in pulsatile LH secretion at the onset of the breeding season were observed in 20 intact, mature Saanen does. Blood was sampled every 20 min for 6 h each week from the beginning of August until the onset of ovulatory activity, as evidenced by cycles in plasma progesterone. The first doe ovulated at the end of August and all were cycling by the end of September. As the first ovulation approached, LH pulse frequency increased by 67% and mean levels of LH increased by 47%. These changes were progressive rather than abrupt. In Exp. 2, seasonal changes in the inhibition of pulsatile LH secretion by ovarian steroids were studied in ovariectomized Saanen does. The animals were untreated (N = 4) or given subcutaneous oestradiol implants (N = 4) and blood was sampled every 10 min for 6 h, twice during the breeding season and twice during the anoestrous season. In each season, the second series of samples was taken after the animals had been treated with progesterone, administered by intravaginal implants. Season did not significantly affect LH secretion in goats not treated with oestradiol, but LH pulse frequency was 54% lower during the anoestrous season than during the breeding season in oestradiol-treated goats. Mean LH concentrations were affected in the same manner as pulse frequency, but pulse amplitude was increased by oestradiol treatment in both seasons. Progesterone had no detectable effect on LH secretion in either season. In Exp. 3, the response to repeated melatonin injections at a set time after dawn was investigated in 11 oestradiol-treated, ovariectomized goats.(ABSTRACT TRUNCATED AT 250 WORDS)     

FACTORS AFFECTING THE SECRETION OF LUTEINIZING HORMONE IN THE EWE

(1) Luteinizing hormone (LH) is secreted as discrete pulses throughout all stages of the reproductive cycle of the ewe, including pre-pubertal, seasonal and lactational anoestrus, and the luteal and follicular phases of the oestrous cycle. Secretion is probably also pulsatile during the preovulatory surge of LH. (2) The secretion of LH is affected by the ovarian steroids, oestradiol and progesterone, both of which act principally to reduce the frequency of the pulses. During the luteal phase the two steroids act synergistically to exert this effect, and during anoestrus oestradiol acts independently of progesterone. Androstenedione secreted by the ovary apparently has no role in the control of LH secretion. (3) The amplitude of the pulses may also be affected by the steroids but there are conflicting reports on these effects, some showing that amplitude is lowered by the presence of oestrogen and others showing increases in amplitude in the presence of oestrogen and progesterone. (4) The secretion of LH pulses is affected by photoperiod, social environment and nutrition. Under the influence of decreasing day-length, oestradiol alone cannot reduce the frequency of pulses and the ewe experiences oestrous cycles. When day-length is increasing, the hypothalamus becomes more responsive to oestradiol which reduces the frequency of the pulses. (5) A hypothetical pheromone secreted by rams can increase the frequency of the LH pulses in anoestrous ewes and thereby induce ovulation, possibly by inhibiting the negative feedback exerted by oestradiol. (6) The relationships between nutrition and reproduction are poorly understood, but it seems likely that the effects of nutrition are mediated partly through the hypothalamus and its control of the secretion of LH pulses. (7) The pulses of LH secreted by the anterior pituitary gland are evoked by pulses of GnRH secreted by the hypothalamus. The location of the centre controlling the GnRH pulses and the neurotransmitter involved are not known.     

Hormonal regulation of oestrogen formation by Leydig cells in vitro: immunocytochemical approach

The ability of the testis to convert androgens into oestrogens is related to the presence of a microsomal enzyme, aromatase, in testicular cells. The aim of this study was to show whether the supplementation of culture media with LH or an aromatase inhibitor could affect the process of aromatisation in Leydig cells of the bank vole in vitro. This was investigated by means of immunocytochemistry and radioimmunological assays. In control cultures of Leydig cells, both steroid hormones secretion as well as immunoreactivities for aromatase and oestrogen receptor were weaker than in those treated with LH. On the contrary, the addition of aromatase inhibitor into the culture medium resulted in a decreased intensity of immunocytochemical stainings in comparison with the control. Concomitantly, the androgen level was slightly higher, whereas that of oestrogen significantly lower than in the control cultures. Additionally, to check whether steroid hormones are able to regulate aromatase or oestrogen receptor immunoexpressions, some of the Leydig cell cultures were enriched with testosterone or oestradiol, respectively. Strong immunoreactivities for both aromatase and oestrogen receptor were observed. This suggests that Leydig cells in vitro are able to regulate directly the secretion of oestrogens by active aromatase. Finally, it is concluded that oestrogen formation in bank vole Leydig cells in vitro can be influenced by various factors. It should be stressed, however, that the effect of hormone stimulation or aromatase inhibitor action appeared to be dependent on the length of light cycles that bank voles were exposed prior to the isolation of Leydig cells.     

Studies on extrahypophyseal sites of estrogen action in the induction of ovulation in rats.

To discover possible extrahypophyseal sites of estrogen action in the induction of ovulation, the influence of a s.c. injection of estradiol benzoate (EB) on cell nuclear sizes in the limbic-medial preoptic continuum of progesterone-pretreated cyclic rats was evaluated. The ovulatory dose of 5 mug EB caused a significant increase of nuclear volumes in the medial preoptic nucleus and the anterior and posterior parts of the medial amygdaloid nucleus. Precocious ovulation was induced in prepuberal female rats by unilateral implantation of a molten EB: cholesterol mixture into the posterior part of the mediocortical amygdala (PMCA), but not by implantation into the anterior part of this region (AMCA) or the medial preoptic area (MPA). In adult females injected s.c. with 2.0 mg progesterone on the day post estrus, bilateral implantation of 0.1 or 0.2 mug crystalline EB on the following day did not abolish the delaying effect of progesterone on the preovulatory LH increase and ovulation, when the implants were located in the MPA, lateral septum (LS), bed nucleus of the stria terminalis (BST), AMCA, PMCA or dorsal hippocampus (DHPC), whereas intrapituitary implants were highly effective. However, the bilateral introduction of large tallow pellets containing 0.1 mug EB each, into the LS, BST, AMCA or PMCA advanced ovulation in rats with progesterone-induced 5-day cycles. Equal pellets did neither induced ovulation nor an LH increase after implantation into the MPA or the DHPC. The results suggest that the anterior pituitary, mediocortical amygdala, BST and LS, but not the MPA or DHPC, are sites of the stimulatory feedback of estrogen on gonadotropin secretion in female rats, and that the amygdaloid response to estrogen differs between prepuberal and cyclic females.     

Effects of RMI 12,936, a synthetic antiprogestational steroid, on the oestrous cycle and ovulation in the rat.

RMI 12,936 inhibited the vaginal cycle and ovulation in the rat. This effect was not mimicked by oestrogen and was partly reversed by progesterone. Ovulation was restored by injection of hCG and the inhibition was associated with reduced cyclic and tonic LH secretion while hypophysial LH levels were generally unaffected. Hypophysial sensitivity to LH-RH was reduced compared with that when ovulation was blocked with sodium pentobarbitone. It is concluded that RMI 12,936 blocks ovulation by causing a reduction in hypophysial sensitivity to LH-RH and that this is probably an antiprogestational effect.     

Effect of dihydrotestosterone on the growth and function of ovarian follicles in intact immature female rats primed with PMSG

Intact, immature female rats were primed with PMSG and treated with 4 injections of DHT. DHT given at 0, 12, 24 and 36 h caused a significant decrease in the ovulation rate 72 h after the PMSG treatment. Concurrent treatment with oestrogen reversed the inhibitory effects of the androgen. The androgen effect was apparently exerted directly on the ovary since DHT did not alter the surge of LH and FSH which occurred at 58 h after PMSG treatment. The DHT inhibition of ovulation was observed in the treatment cycle as well as in subsequent cycles which followed a second PMSG injection. This finding suggests that intermediate size follicles were also adversely affected by the androgen. To confirm that androgen affects follicles of all size ranges, follicles less than 200 microns, 200-400 microns and greater than 400 microns in diameter were isolated from the ovaries of rats treated with PMSG and DHT or the vehicle. The follicles were isolated by density gradient separation of follicles followed by filtration with pre-calibrated Teflon sieves. In some experiments, granulosa cells were also harvested from isolated follicles. DHT treatment did not affect the numbers of follicles of any size but did reduce the oestrogen content of follicles of all sizes. Follicles from DHT-treated animals contained fewer granulosa cells and the cells from treated animals had lower aromatase activity than did cells from control rats. Taken together, these findings suggest that DHT reduces the ovulation rate by decreasing the number of granulosa cells/follicle and by altering the oestrogen synthetic abilities of the cells. All follicles, regardless of size, were sensitive to androgen treatment.     

Effect of pentobarbitone sodium and bromocriptine on follicular oestradiol production in the rat

Injection of an ovulation-blocking dose of pentobarbitone sodium given in the early afternoon of pro-oestrus in rats decreased follicular oestradiol production in vitro the next day (2.42 +/- 0.11 ng/4 h/follicle in pro-oestrous rats, 0.49 +/- 0.04 ng/4 h/follicle in pentobarbitone-treated rats). Pentobarbitone, given 1 day earlier (at dioestrus II), prevented the increase in oestradiol production that normally occurs between di-oestrus II and pro-oestrus. Injection of a subovulatory amount of hCG (0.5 i.u.) given after pentobarbitone injection inhibited the decrease in follicular oestradiol production induced by pentobarbitone. The pentobarbitone-induced decrease in oestradiol production was also prevented by bromocriptine (1 mg) given at di-oestrus II (15:00 h) and pro-oestrus (09:00 h). Bromocriptine is an effective inhibitor of prolactin secretion and this suggests therefore that the decrease in follicular oestradiol production after pentobarbitone is due to the preovulatory surge of prolactin. However, pretreatment with bromocriptine also inhibited the effect of pentobarbitone on oestradiol production when pentobarbitone was given at di-oestrus II. Moreover, when ergocornine (another inhibitor of prolactin secretion) was used instead of pentobarbitone to block ovulation, follicular oestradiol production was also decreased the next day. In contrast to bromocriptine, ergocornine was not able to prevent the pentobarbitone-induced decrease in follicular oestradiol production. These results indicate that the decrease in follicular oestradiol production after pentobarbitone injection is due to inhibition of the serum concentrations of LH rather than the preovulatory surge of prolactin. How bromocriptine (but not ergocornine) prevents the pentobarbitone-induced decrease in oestradiol production is not clear.     

Differential changes in the mechanisms controlling luteinizing hormone and prolactin secretion in middle-aged female rats

Serum luteinizing hormone (LH) and prolactin (PRL) concentrations were measured in young (3-4 month old) and middle-aged (10-12 month old) intact female rats on proestrus, in ovariectomized rats after two estrogen injections (estradiol benzoate; EB, 10 micrograms/100 g body weight, s.c.) or after preoptic stimulation in EB-primed ovariectomized rats. Only animals showing regular 4-day estrous cycles were selected for the experiment. The magnitude of proestrous LH surge was significantly smaller in middle-aged than in young rats. Two BE injections, at noon on Days 0 and 3, in ovariectomized middle-aged rats failed to induce surges in LH secretion on Day 4 whereas the same treatment produced LH surges in ovariectomized young rats. The preoptic electrochemical stimulation (50 microA for 60 sec) produced a prompt rise in serum LH levels in ovariectomized EB-primed young but not in middle aged rats. The preoptic stimulation with a larger current (200 microA) induced LH secretin in middle-aged rats. In none of these situations serum PRL concentrations were different between young and middle-age rats. These results suggest differential aging rates in the preoptic mechanisms governing LH and PRL secretion in the rat. The function of the preoptic ovulatory center in responding to the estrogen positive feedback action and inducing LH secretion may become impaired and independent of the PRL control mechanism, even before the regular estrous cycle terminates.     

On the evocability of a positive oestrogen feedback action on LH secretion in transsexual men and women.

In transsexual men with homosexual behaviour and intact testicular function, as well as in homosexual men with normal gender identity, following a negative oestrogen feedback effect a delayed positive oestrogen feedback action on LH secretion was evoked. By contrast, in transsexual men with hypo- or asexuality and intact testes or hypergonadotrophic hypo- or agonadism, as well as in heterosexual men with normal gender identity, a negative oestrogen feedback effect was not followed by a positive feedback action on LH release. In transsexual women with homosexual behaviour and oligo- and/or hypomenorrhoea, only a weak or at best moderate positive oestrogen feedback action on LH release was evocable, similarly as in castrated and oestrogen-primed heterosexual men. By contrast, in a transsexual woman with bisexual behaviour and eumenorrhoea, a strong positive oestrogen feedback action on LH secretion was evocable, as well as in heterosexual women with normal gender identity.     

Delta-9-tetrahydrocannabinol attenuates luteinizing hormone release induced by electrochemical stimulation of the medial preoptic area.

Despite diverse pharmacological actions, drugs commonly used for blocking ovulation in the rat have not been observed to exert differential effects on the LH response to preoptic stimulation, thus suggesting blocking action above the final hypothalamic GnRH pathway. To determine if ovulatory blockade by delta-9-tetrahydrocannabinol (THC) is consistent with that scheme, LH surges evoked by preoptic stimulation were contrasted with those elicited during blockade by atropine (ATR), a classic ovulation-blocking agent with which other drugs have been compared. THC (10 mg/kg) or ATR (350 mg/kg) treatment before the proestrous critical period uniformly blocked LH release and ovulation in sham-stimulated rats. Preoptic stimulation evoked LH surges after both drug treatments (p less than 0.001), peak levels increasing with the intensity of stimulation (p less than 0.05). However, both maximum LH concentration (p less than 0.05) and total integrated LH release (p less than 0.01) were lower in THC-blocked rats. Inspection of the oviducts revealed no difference in the incidence of ovulation or the number of ova discharged. The reduced LH response during THC blockade was not attributable to variation in the extent or locus of histologically determined stimulation sites. These results distinguish THC from ATR and, by extension, other blocking drugs that do not overtly affect the LH response to preoptic stimulation. Thus, ovulatory blockade by THC may involve a different mechanism, which likely includes inhibitory action within the preoptic-to-tuberal GnRH pathway.     

Nuclear association states of rat uterine oestrogen receptors as probed by nuclease digestion

The solubilization of oestrogen receptors from uterine nuclei by micrococcal nuclease and deoxyribonuclease I was examined after the injection of oestradiol or Nafoxidine into castrated female rats. At 1h after an injection of oestradiol, 30% (0.18pmol/mg of DNA) of the nuclear oestrogen receptors was solubilized by 5 min of mild digestion with either nuclease. No further receptor release occurred, although DNA hydrolysis continued throughout a 20min interval. The limitation in receptor solubilization was not due to an artifact of digestion conditions or insufficient nuclease concentrations. Similar patterns of receptor solubilization and DNA hydrolysis were obtained with both nucleases whether the animals had been injected with oestradiol 1h before death or if the uteri from uninjected animals were incubated with [(3)H]oestradiol for 1h in vitro. When uterine nuclei were digested with these enzymes 12h after the animal was injected with oestradiol there was little change in the quantity of nuclease-sensitive sites (0.11pmol/mg of DNA); however, the quantity of nuclease-resistant sites decreased 10-fold. These values correspond quantitatively to the changes in salt-resistant and salt-extractable sites observed over a 12h interval after oestradiol treatment. Nuclease digestion of uterine nuclei obtained 16h after Nafoxidine treatment gave a pattern qualitatively and quantitatively similar to that observed 1h after oestradiol treatment, a result consistent with the agonist/antagonist action of this compound. An analysis by sucrose-density-gradient centrifugation of the time course of nuclease-dependent receptor solubilization indicated that the solubilized receptors were not associated with discrete nucleosomal fragments. We believe that these data indicate that only a portion of the receptors translocated to the nucleus become associated with chromatin, and this association may occur on regions of chromatin that are preferentially susceptible to nucleolytic cleavage.     

Evocability of a slight positive oestrogen feedback action on LH secretion in castrated and oestrogen-primed men.

Orchidectomized heterosexual men suffering from prostatic cancer with suppressed serum LH values by oestrogen priming exhibited a slight, but significant surge of LH secretion following oestrogen injection. In contrast, orchidectomized and oestrogen-primed heterosexual men with unsuppressed serum LH levels as well as intact heterosexual men did not display any positive oestrogen feedback action on LH secretion, as it was observed in intact homosexual men.     

Hypothalamic responsiveness to oestrogen in hypothyroid rats.

When 50 iu of PMS is given at 28 days of age, ovulation occurs on day 31, in thyroidectomized rats receiving PMS at 28 days of age, ovulation appears on day 30 and 31. PMS treated thyroidectomized rats were given 0.5 mug oestrogen at 9 a.m. on day 29 or 30. Injection on day 29 increases ovulation, but the injection of day 30 has no effect. Injection of 1.0 mug oestrogen on day 29 reduces activity, however, 1.0 mug on day 30 increases ovulation. These results infer than the hypothyroid state in PMS-treated rats significantly alters hypothalamic responsiveness to oestrogen.