Priming Effect of Luteinizing Hormone Releasing Factor Elicited by Preoptic Stimulation and by Intravenous Infusion and Multiple Injections of the Synthetic Decapeptide

Abstract

We have investigated whether the priming effect of LH-RF can be elicited by electrical stimulation of the medial preoptic area, or by i.v. infusion or multiple i.v. injections of the synthetic decapeptide. All experiments were carried out on animals anaesthetized with sodium pentobarbitone at 13.30 h. In pro-oestrous rats, the LH response to the second of two electrical stimuli, 15 min in duration and separated by 60 min, was significantly greater than the response to the first stimulus. When synthetic LH-RF was infused at a constant rate for 90 min, plasma LH increased gradually for the first 45-60 min after which it increased markedly. This enhanced secretion of LH did not occur in rats which were infused with the same total dose of LH-RF, either 15 or 75 ng/100 g body wt, over periods of 45 min or less. When a dose of 15 ng LH-RF/100 g body wt was administered in six divided doses by i.v. injections, each separated by 15 min, there was a marked increase in plasma LH after 75 min. The profile of the mean plasma LH concentration in rats subjected to preoptic stimulation for 90 min was similar to that in rats infused for 90 min with LH-RF, but the variation in response was much greater in the stimulated rats. These results indicate that the priming effect can be elicited by endogenous as well as synthetic LH-RF, and that whether LH-RF reaches the pituitary at a constant rate or in a pulsatile manner the factor is capable of significantly increasing the responsiveness of the gonadotrophs. The relevance of these findings with respect to the development of the spontaneous preovulatory LH surge is discussed. A priming effect could not be elicited by constant LH-RF infusion in dioestrous rats; this supports the view that steroid hormones, especially oestradiol-17phi, determine the magnitude of the effect. The LH response in male rats subjected to i.v. infusion of LH-RF was much lower than in females. Pre-treatment with oestradiol benzoate did not increase the response significantly, suggesting that this sex difference cannot be ascribed simply to low levels of plasma oestrogen in the male.

The effect of LH-RH administration on LH release in the female rabbit

“…Although our approach by infusion may have more closely simulated the pattern of endogenous LH-RH secretion before ovulation in this species (Tsou et al, 1977), it is also possible that the initial dose of releasing hormone (100 ng) produced a priming effect that resulted in a much larger LH release during the second hour of infusion. A priming effect, in which subsequent injections of LH-RH evoke a greater release of LH, has been demonstrated previously in the rat (Fink, Chiappa & Aiyer, 1976) and ewe (Crighton & Foster, 1977 (Cooper et al, 1973;Gordon & Reichlin, 1974;Ferland, Borgeat, Labrie, Bernard & DeLean, 1975;Legan & Karsch, 1975). This change appears to be related to the effects of oestrogen on the anterior pituitary, because circulating levels of endogenous oestradiol-17ß increase at this time (Butcher, Collins & Fugo, 1974) and pretreatment with oestradiol benzoate raises the amount of LH released by LH-RH treatment in dioestrous (Arimura & Schally, 1971) and ovariectomized (Libertun, Cooper, Fawcett & McCann, 1974) rats.…”

Pituitary self-priming actions of gonadotropin-releasing hormone. Kinetics of estradiol's potentiating effects on gonadotropin-releasing hormone-facilitated luteinizing hormone and follicle-stimulating hormone release in healthy postmenopausal women.

“…Thus, estimated total LH and FSH release in response to exogenous paired GnRH pulses varies significantly in relation to the duration of estradiol replacement. factor exemplifies the self-priming action of GnRH (1)(2)(3)(4)(5). Our appraisal of the detailed time-course of estradiol's influence on this self-potentiating action of GnRH indicates the dynamic nature of estrogen action, which is characterized by the emergence of maximal GnRH self-priming within 5-10 d of increased circulating estradiol concentrations, followed by an attenuation of GnRH self-priming after 30 d of continuous estradiol exposure.…”

“…Under certain physiological conditions, repetitive stimulation of the anterior pituitary gland by serial pulses of gonadotropinreleasing hormone (GnRH)' results in marked potentiation of gonadotropin release (1)(2)(3)(4)(5). This ability of repetitive GnRH stimulation to facilitate pituitary responsiveness has been referred to as the "self-priming" action ofthis hypothalamic decapeptide (1).…”

“…This ability of repetitive GnRH stimulation to facilitate pituitary responsiveness has been referred to as the "self-priming" action ofthis hypothalamic decapeptide (1). Studies in a variety of experimental animals have suggested that such amplifying effects of serial GnRH stimulation may be critically important to the genesis of the preovulatory surge-like release of gonadotropic hormones during the final stages of follicular development (1)(2)(3)(4)(5)(6)(7)(8).…”

Relationship Between Duration of Urethane or Pentobarbitone Anaesthesia in Male and Female Rats and Adenohypophyseal Response to Luteinising Hormone‐releasing Hormone

“…Some evidence for this suggestion is provided by the finding that the urethane-treated female rats showing the greatest response to LH-RH had slightly higher pre-injection concentrations of plasma LH than the equivalent pentobarbitoneanaesthetized rats. Potentiation of the pituitary response to LH-RH by previous exposure to this peptide occurs most readily in pro-oestrous rats (Fink, Chiappa & Aiyer, 1976) and this may be a reason for the different effects of urethane on the pituitary responsiveness to exogenous LH-RH described in this paper.…”