LH-releasing activity

Similarly prepared extracts of cerebral cortex were ineffective which indicated that the action of h3rpothalamic extracts was a specific one. Extraction of various hypothalamic areas revealed that the major LH-releasing activity was concentrated in the SME region. There was minimal activity in the overlying ventral hypothalamus (2). At this point the unknown substance responsible for the LH-releasing effect was designated LRF. 

Since the immature test rats used in evaluating LH-releasing activity were treated with large doses of gonadotrophins and had relatively low stores of hypophysial LH (2,6), it was advisable to determine if LH-releasing activity could be demonstrated in more physiological circumstances. The LH-releasing action of hypothalamic extracts has now been evaluated in a variety of test animals. 

Recently a fraction was recovered in each of the 5 fractionations of ovine SME with Sephadex which blocked the suckling-induced release of prolactin (Fig. 4). This fraction was separated from FSH, STH, MSH and TSH releasing factors and from vasopressin but was found to be closely associated with LH-RF as judged by the ovarian ascorbic acid depletion assay. However, in 3 of 5 experiments there was a tendency for PIF to be eluted just prior to the peak of LH-releasing activity. It is important to note that Schally et. al. (32) reported that LH-RF fractions from their Sephadex column were devoid of PIF when tested as to their ability to inhibit prolactin release in vitro. Arimura et. al. (33) found that purified porcine LH-RF was iivoTd of PIF activity as judged by its inability to block the release of prolactin in response to cervical probing in the rat. 

Progesterone produces direct membrane effects [16]. These include actions that promote maturation of spermatozoa as well as oocytes and facilitation of the release of neurotransmitters such as dopamine and LH-releasing hormone (LHRH) (Fig. 52-7). Membrane actions of progesterone also activate oxytocin receptors in the hypothalamus in a way that enables oxytocin to turn on sexual behavior in the estrogen-primed female rat [3],... 

LH-RH 31, isolated in 1971 by Schally et al. 67) and in 1974 by Guillemin from porcine and sheep hypothalamus tissue, possesses LH-releasing and FSH-releasing activity and is available commercially as Lutal 68). 

DAGs have been shown to stimulate a Ca2+-dependent protein kinase (PKC) by increasing the affinity of this enzyme for phospholipids and Ca2+ [95,96]. Initial evidence for a similar mechanism in the GnRH stimulus transmission was obtained from experiments in which phorbol dibutyrate and phorbol 12-myristate 13-acetate were able to stimulate LH release [53,97,98]. This stimulatory effect of phorbol esters is probably caused by binding and activation of PKC, thereby mimicking endogenous DAGs [99]. 

In order to obtain more direct evidence for an activational role of DAGs on PKC, water soluble DAGs were synthesized and added to pituitary cells [100]. Synthetic DAGs which had an acyl chain length between 4 and 10 carbons in the sn-1 and 2 position were able to stimulate PKC activity as well as LH release. Struc-... 

He J-R, Molnar J, Barraclough CA (1994) Evidence that amplification of norepinephrine-induced LH release by morphine is indirectly due to suppression of tuberoinfundibular dopamine secretion. Brain Res 652 1-8. Hentschel K, Cheung S, Moore KE, Lookingland KJ (1998) Pharmacological evidence that neurotensin mediates prolactin-induced activation of tuberoinfundibular dopamine neurons. Neuroendocrinology 65 71-76. Hentschel K, Will YM, McMahon CD, Moore KE, Lookingland KJ (1999) Prolactin induces Fos-related antigen expression in neurotensin (NT)-IR neurons and increases numbers of NT-IR neurons in the arcuate nucleus. Soc Neurosci Abstr 25 1185. 

Kalia V, Fenske C, Hole DR, Wilson CA (1999) Effect of gonadal steroids and gamma-aminobutyric acid on LH release and dopamine expression and activity in the zona incerta in rats. J Reprod Fertil 777 189-197. 

MacKenzie FJ, James MD, Wilson CA (1988) Changes in dopamine activity in the zona incerta (ZI) over the rat oestrous cycle and the effect of lesions of the ZI on cyclicity further evidence that the incerto-hypothalamic tract has a stimulatory role in the control of LH release. Brain Res 444 75-83. 

The large bolus of LH released (preovulatory LH surge) in response to positive feedback by estradiol induces ovulation in about 1 day, probably by stimulation of production of granulosa plasminogen activator, which leads to formation of plasmin, an enzyme that may be responsible for the digestion of the basal lamina and, consequently, for the rupture of the follicle (ovulation). 

Progesterone decreases the frequency of GnRH pulses and also exerts a direct pituitary effect to oppose the inhibitory actions of estrogens and thus enhance the amount of LH released. These steroid feedback effects, coupled with the intrinsic activity of the GnRH neurons, lead to relatively frequent LH pulses of small amplitude in the follicular phase, and less frequent pulses of larger amplitude in the luteal phase. 

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