P. Landis Keyes

Repeated Exposure to Prolactin Is Required to Induce Luteal Regression in the Hypophysectomized Rat

Abstract We investigated whether prolactin (PRL) treatments resembling the intermittent PRL surges of estrous cycles could induce luteal regression in hypophysectomized rats. Immature female rats were stimulated to ovulate and form corpora lutea with exogenous gonadotropins, and were hypophysectomized following ovulation. A single s.c. injection of either vehicle (VEH) or PRL was administered to each rat on post-hypophysectomy Day 8 and again on Day 11. The four resulting treatment groups consisted of rats that received two injections of VEH, VEH followed by PRL, PRL followed by VEH, or two injections of PRL. Rats were killed 24 or 72 h following the second injection. Plasma 20α-dihydroprogesterone, luteal weight, and total luteal protein were determined. One ovary was sectioned for immunohistochemistry for monocytes/macrophages, apoptotic nuclei, and major histocompatibility class II (MHC II) molecules. No effect of time (following injection) was observed on any endpoint, indicating that PRL does not have an ongoing regressive action. Time groups from within each treatment group were therefore pooled for analysis. Significant declines (P < 0.05) in plasma concentrations of 20α-dihydroprogesterone, luteal weight, and protein per corpus luteum occurred only after two injections of PRL. Numbers of luteal monocytes/macrophages, apoptotic nuclei, and MHC II-positive cells were low in all groups; numbers of luteal monocytes/macrophages increased following two injections of PRL (P < 0.05). We conclude that PRL has a cumulative regressive effect on the corpus luteum of the hypophysectomized rat. Drawing a parallel with the estrous cycle, we suggest that continued exposure to PRL, over several cycles, is necessary to induce full luteal regression.

Role of Estrogen and the Placenta in the Maintenance of the Rabbit Corpus Luteum

The rabbit is among those species in which the placenta secretes low or physiologically insignificant quantities of progesterone, and therefore, the corpora lutea must remain steroidogenically active throughout gestation (Hilliard, 1973; Thau and Lanman, 1974). If the young embryo is to survive, it must transmit a signal that in some way halts or overrides incipient luteal regression, reflected in declining serum progesterone values by 15 days after ovulation in non-pregnant animals (Keyes et al., 1983a). The subject of this manuscript is an exploration of the mechanisms that are responsible for placental maintenance of luteal function. We begin with a brief summary of the literature, setting the stage for the specific hypotheses and experiments reported herein.

New Perspectives on the Endocrine Regulation of the Rabbit Corpus Luteum

In many species a luteotrophic hormone has been identified which maintains the morphological and functional integrity of the corpus luteum. For example, in large domestic animals and in primates LH is thought to have the preeminent role as the luteotrophic hormone (Hansel et al., 1973; Niswender et al., 1980; Knobil, 1973), and prolactin is recognized as the major luteotrophic hormone in the rat (Rothchild, 1981). However, it has become evident that other hormones can act upon the corpus luteum, and thus potentially have a significant influence upon steroidogenic activity as well as lifespan of the gland. To illustrate this feature, progesterone synthesis can be stimulated in cow and sheep corpora lutea by catecholamines in vitro, and this action, at least in sheep, is directly upon steroidogenic luteal cells (Jordan et al., 1978; Condon and Black, 1976). The ultimate control of steroidogenesis in sheep luteal cells is unclear in view of the recent observation that the large luteal cells, which comprise the major progesterone secretory component of the ovine corpus luteum in vivo, exhibit no steroidogenic response either to LH or to elevated cyclic AMP (Fitz et al., 1982; Hoyer et al., 1983). The rat corpus luteum passes through an LH-sensitive period which is thought to be mediated by estrogen produced within the corpus luteum (Gibori et al., 1977; 1978). In the rabbit, 17β-estradiol of follicular origin is considered the essential luteotrophic hormone (Keyes et al., 1983), although the luteal tissue is clearly responsive to LH (Dorrington and Kilpatrick, 1969; Hunzicker-Dunn and Birnbaumer, 1976) and also possesses a catecholamine sensitive adenylyl cyclase (Hunzicker-Dunn, 1982).