Barbiturate Anesthesia Blocks the Positive Feedback Effect of Progesterone, but not of Estrogen, on Luteinizing Hormone Release in Ovariectomized Guinea Pigs*

162

The direct pituitary effects of estrogen and progesterone on the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were studied in ovariectomized (OVX) ewes in which the pituitary had been disconnected surgically from the hypothalamus (hypothalamo-pituitary disconnection, HPD). Gonadotropin secretion was restored with hourly pulses of 500 ng gonadotropin-releasing hormone (GnRH) via intra-atrial cannulae. Intramuscular injections of 50 µg estradiol benzoate (EB) to 5 sheep initially caused reductions (∼5O%) in plasma LH baseline, peak values and LH pulse amplitude. Therafter all parameters of plasma LH concentration increased 2- to 3-fold above starting values. After these 5 sheep had received 2 subcutaneous progesterone implants (mean ± SEM plasma levels 5.3 ± 1.5 nmol/1), the biphasic LH response to EB was still apparent and increases in LH peak values (267 ± 19%) and LH pulse amplitudes (262 ± 23%) were greater (p < 0.05) than those seen with EB alone (195 ± 11 and 172 ± 14%, respectively). The presence of 2 progesterone implants alone did not change plasma LH baseline, peak values or pulse amplitude, or plasma FSH values. In the second experiment, where 4 OVX-HPD ewes were given 4 progesterone implants (plasma progesterone 27.7 ± 3.4 nmol/l), there were no effects on basal plasma LH or plasma FSH values. The LH responses to EB were more marked in 4 OVX-HPD ewes given 4 progesterone implants than in the animals given EB alone. Also, the estrogen-induced LH surge occurred earlier in the ewes given 4 progesterone implants than in those given estrogen alone. The addition of 2 or 4 subcutaneous progesterone implants did not affect estrogen-induced suppression of FSH secretion in GnRH-pulsed OVX-HPD ewes. These data indicate that estrogen has a direct pituitary effect to influence the action of GnRH and that progesterone alone does not influence the secretion of LH or FSH by a direct pituitary effect. Progesterone may enhance the feedback effects of estrogen on LH secretion by a direct action at the pituitary level.

Section: Discussionmentioning

confidence: 99%

Direct Pituitary Effects of Estrogen and Progesterone on Gonadotropin Secretion in the Ovariectomized Ewe

Clarke¹,

Cummins

1984

162

“…estrogen must be present prior to 14.00-16.00 h, the time at which cyclic GnRH and LH re lease first appears [6,34,35,37]. Finally, there are several indications that the neurogenic signal for GnRH release is estrogen-independent and occurs daily at about this time of day [6,21,22,38], Although continuous 24+ h estrogen treatments were the most effective stimuli eliciting cyclic LH secretion, shorter exposures of 7-18 h duration did induce discernible LH dis charges. Similarly, two 3-hour exposures separated by 12-or 18-hour intervals also stimulated LH release.…”

Section: Discussionmentioning

confidence: 99%

“…At the present time, we do not know the mechanisms underlying each of the species differences. They simply may reflect the absence/presence of a neurogenic, circadian signal which times the LH release [6,7,12,18,21,22,38]. On the other hand, these differences may reflect different sites or mechanisms of steroid action within the brain-pituitary complex.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Estrogen Stimuli Sufficient to Initiate Cyclic Luteinizing Hormone Release in Acutely Ovariectomized Rats

Krey¹,

Parsons²

1982

Estradiol (E)-filled Silastic capsules were implanted subcutaneously to characterize the estrogen stimulus sufficient to initiate cyclic LH secretion in female rats ovariectomized on diestrus 1 of the estrous cycle. Such capsules elevate preoptic area, hypothalamic and hypophysial cell nuclear estrogen receptor levels to proestrous values within ½ h following insertion; upon removal of the capsules, nuclear receptor levels decline monotonically to ovariectomized control levels by 8 h in brain and 12 h in pituitary. Three parameters of the E stimulus were studied:latent period, duration, and continuity. E stimuli, short in duration (7–12 h) and discontinuous in nature (3 h pulses 12 or 15 h apart), effectively stimulated LH surges on ‘proestrus’. However, these stimuli had to begin 30 h prior to the onset of LH release. Such a latent period for estrogen action was not observed when we monitored the ability of the same E stimuli to enhance pituitary responsiveness to GnRH. These studies demonstrate that the ‘rate-limiting step’ for estrogen’s positive feedback action is located within the estrogen-sensitive brain circuits controlling GnRH release and defines the temporal characteristics of E stimuli activating these circuits.

“…Conversely, additional administra tion of progesterone induces a large LH surge followed by inhibition [10,19]. Furthermore, estrogen, not progeste rone, is thought to be the hormonal stimulus necessary and sufficient for phasic gonadotropin release [10,12], and it has been suggested that estrogen and progesterone act at different levels of the hypothalamo-hypophysial axis to in duce gonadotropin release [11,24,35], Therefore, the pre sent study was undertaken to test the possibility that a com mon deficit in an estrogen-sensitive gonadotropin-releasing mechanism is the cause of persistent estrus. Small electrolyt ic lesions were made at various points along the rostrocaudal extent of the suprachiasmatic region in female rats and the effect on estrous cyclicity and spontaneous ovulation was observed.…”

mentioning

confidence: 99%

Discrete Lesions Reveal Functional Heterogeneity of Suprachiasmatic Structures in Regulation of Gonadotropin Secretion in the Female Rat

Wiegand¹,

Terasawa²

1982

Self Cite

336

192

The present study examines the function of several cytologically distinct suprachiasmatic structures in the regulation of ovulation and positive feedback effects of estrogen and progesterone on gonadotropin release in the rat. Small (0.6–0.8 mm dia.) electrolytic lesions were placed at four loci along the rostrocaudal extent of the suprachiasmatic region in regularly cycling female rats. Anovulatory persistent estrus occurred only when lesions were located either in the suprachiasmatic nucleus (SCN) or the medial preoptic nucleus (MPN), a small periventricular cell group lying immediately caudal to the organum vasculosum lamina terminalis (OVLT). Lesions restricted to the OVLT and adjacent ventral prechiasmatic region (VPC-L), or the anterior suprachiasmatic region (ASR) between the MPN and SCN resulted in irregular estrous cycles frequently marked by periods of prolonged diestrus. Following administration of 50 µg estradiol benzoate (EB) a daily afternoon surge of gonadotropin was observed in control animals. This circadian release of gonadotropins was completely abolished by SCN, ASR and MPN lesions. EB-induced gonadotropin surges were also greatly attenuated by VPC-L lesions. Subsequent administration of 1.5 mg progesterone (P) induced large surges of luteinizing hormone and follicle-stimulating hormone in VPC-L and ASR lesioned animals as well as controls. P administration also elicited gonadotropin surges in SCN lesioned animals, although surges were markedly attenuated in magnitude compared to controls. Only lesions that destroyed the MPN and immediately adjacent periventricular tissue completely and invariably eliminated P-induced gonadotropin release. Thus, anovulatory persistent estrus appears to be associated specifically with lesions that interfere with the positive feedback effect of P (MPN and SCN lesions). Animals with lesions that block or attenuate EB effects without interfering with P sensitive neural substrates can maintain long-term spontaneous ovulation (VPC-L and ASR lesions). An hypothesis is advanced to account for the differential effect of MPN and SCN lesions on P-induced gonadotropin release.