Prolactin is a protein hormone of the anterior pituitary gland that was originally named for its ability to promote lactation in response to the suckling stimulus of hungry young mammals. We now know that prolactin is not as simple as originally described. Indeed, chemically, prolactin appears in a multiplicity of posttranslational forms ranging from size variants to chemical modifications such as phosphorylation or glycosylation. It is not only synthesized in the pituitary gland, as originally described, but also within the central nervous system, the immune system, the uterus and its associated tissues of conception, and even the mammary gland itself. Moreover, its biological actions are not limited solely to reproduction because it has been shown to control a variety of behaviors and even play a role in homeostasis. Prolactin-releasing stimuli not only include the nursing stimulus, but light, audition, olfaction, and stress can serve a stimulatory role. Finally, although it is well known that dopamine of hypothalamic origin provides inhibitory control over the secretion of prolactin, other factors within the brain, pituitary gland, and peripheral organs have been shown to inhibit or stimulate prolactin secretion as well. It is the purpose of this review to provide a comprehensive survey of our current understanding of prolactin's function and its regulation and to expose some of the controversies still existing.

/pdf/prolactin-structure-function-and-regulation-of-secretion-3w4x6fqbg3.pdf

Prolactin: Structure, Function, and Regulation of Secretion

The short length of the estrous cycle of rats makes them ideal for investigation of changes occurring during the reproductive cycle. The estrous cycle lasts four days and is characterized as: proestrus, estrus, metestrus and diestrus, which may be determined according to the cell types observed in the vaginal smear. Since the collection of vaginal secretion and the use of stained material generally takes some time, the aim of the present work was to provide researchers with some helpful considerations about the determination of the rat estrous cycle phases in a fast and practical way. Vaginal secretion of thirty female rats was collected every morning during a month and unstained native material was observed using the microscope without the aid of the condenser lens. Using the 10 x objective lens, it was easier to analyze the proportion among the three cellular types, which are present in the vaginal smear. Using the 40 x objective lens, it is easier to recognize each one of these cellular types. The collection of vaginal lavage from the animals, the observation of the material, in the microscope, and the determination of the estrous cycle phase of all the thirty female rats took 15-20 minutes.

/pdf/determination-of-the-estrous-cycle-phases-of-rats-some-23l4r6irnl.pdf

Determination of the estrous cycle phases of rats: some helpful considerations

We have found that the density of synapses in the stratum radiatum of the hippocampal CA1 region in the adult female rat is sensitive to estradiol manipulation and fluctuates naturally as the levels of ovarian steroids vary during the 5 d estrous cycle. In both cases, low levels of estradiol are correlated with lower synapse density, while high estradiol levels are correlated with a higher density of synapses. These synaptic changes occur very rapidly in that within approximately 24 hr between the proestrus and estrus stages of the estrous cycle, we observe a 32% decrease in the density of hippocampal synapses. Synapse density then appears to cycle back to proestrus values over a period of several days. To our knowledge, this is the first demonstration of such short-term steroid-mediated synaptic plasticity occurring naturally in the adult mammalian brain.

https://www.jneurosci.org/content/jneuro/12/7/2549.full.pdf

Estradiol mediates fluctuation in hippocampal synapse density during the estrous cycle in the adult rat.

We have used Golgi-impregnated tissue to demonstrate that apical dendritic spine density in CA1 hippocampal pyramidal cells undergoes a cyclic fluctuation as estradiol and progesterone levels vary across the estrous cycle in the adult female rat We observed a 30% decrease in apical dendritic spine density over the 24-hr period between the late proestrus and the late estrus phases of the cycle Spine density then appears to cycle back to proestrus values over a period of several days In contrast, no significant changes in dendritic spine density across the estrous cycle occur in CA3 pyramidal cells or dentate gyrus granule cells These results demonstrate rapid and ongoing dendritic plasticity in a specific population of hippocampal neurons in experimentally unmanipulated animals

/pdf/naturally-occurring-fluctuation-in-dendritic-spine-density-390tvlir2x.pdf

Naturally occurring fluctuation in dendritic spine density on adult hippocampal pyramidal neurons

We have previously shown that the density of dendritic spines on hippocampal CA1 pyramidal cells is dependent on circulating estradiol and progesterone and fluctuates naturally during the 5 day estrous cycle in the adult rat. To date, however, no detailed characterization of the roles that these hormones play in regulation of spine density has been made. In order to determine the time courses and extent of the effects of estradiol and progesterone on dendritic spine density, we have analyzed the density of dendritic spines on the lateral branches of the apical dendritic tree of Golgi-impregnated CA1 hippocampal pyramidal cells in several experiments. In summary, our findings included the following: (1) Following ovariectomy, circulating estradiol is undetectable within 24 hours; however, spine density decreases gradually over a 6 day period. (2) Spine density does not decrease any further up to 40 days following ovariectomy. (3) Treatment with estradiol alone can reverse the ovariectomy-induced decrease in spine density. (4) Spine density begins to increase within 24 hours following estradiol benzoate injection in an ovariectomized animal, peaks at 2 and 3 days, then gradually decreases over the next 7 day period. (5) Although free estradiol is metabolized more rapidly than estradiol benzoate, there is no difference in the rate of decrease in spine density following injection of either form. (6) Progesterone has a biphasic effect on spine density in that progesterone treatment following estradiol initially increases spine density for a period of 2 to 6 hours but then results in a much sharper decrease than is observed following estradiol alone. By 18 hours following progesterone treatment, spine density is decreased nearly to 6 day ovariectomy values. (7) Treatment of intact rats with the progesterone receptor antagonist, RU 486, during the proestrus phase of the estrous cycle inhibits the proestrus to estrus drop in spine density. These findings account for both the gradual increase and rapid decrease in spine density which we have previously observed during the estrous cycle and indicate that progesterone in particular may be an important factor in the regulation of rapid morphologic changes which occur naturally in the adult brain. © 1993 Wiley-Liss, Inc.

Roles of estradiol and progesterone in regulation of hippocampal dendritic spine density during the estrous cycle in the rat

The hormonal factors associated with converting a corpus luteum of estrous cycle into a corpus luteum of pseudopregnancy were studied by measuring LH and FSH prolactin, estradiol and progesterone levels in decapitated rats during the 4-day estrous cycle and a comparable time of pseudopregnancy (lights on 0600-0800 hr.). During the estrous cycle, prolactin, LH and FSH remained low and unchanging except on the afternoon of proestrus, when typical proestrous surges were observed. In contrast, estradiol levels began to increase on D-1, from baseline values of 7 pg/ml to approximately 15-20 pg/ml. These levels were maintained until the afternoon of D-2 when estradiol further increased to reach peak levels of 40-50 pg/ml by 0900 hr on proestrus. Estradiol then declined in relation to the increase in LH secreation and had returned to baseline by estrus. Progesterone secretion by the corpora lutea of the cycle also increased on the afternoon of D-1 and reached a maximum value of 25-30 ng/ml early on the morning of D-2. At this time, a precipitious fall in progesterone occurred, returning to baseline values of 5-1- ng/ml by 0700 on D-2 signifying the regression of the corpora lutea of the cycle. Progesterone remained low thereafter until the afternoon of proestrus when levels increased in response to the proestrus when levels increased in response to the proestrous surge of LH. Following cervical stimulation at 1900 hr on proestrus, no differences were noted, with respect to the estrous cycle, in LH, FSH or estradiol secreation through the afternoon of D-2. Surprisingly, progesterone levels did not differ in the cycle and pseudopregnancy until the early morning of D-29 instead of progesterone levels falling to baseline as they had during the cycle, the corpora lutea of pseudopregnancy were rescused, progesterone increasing dramatically to reach levels of 45-50 ng/ml by 1700 hr on that same day. The only difference in hormone secretion that was noted which could account for this marked divergence in progesterone secretion was the pattern of prolactin secretion following cervical stimulation. In contrast to the low levels seen during the estrous cycle, biphasio surges of prolactin secretion occured each day, one being nocturnal (0100-0900 hr) and the other diurnal (1500-2100 hr). The rescue of the corpus luteum occured in association with the nocturnal surge on D-2. These results suggest that nocturnal surge on D-2, PROLACTIN IS THE MAJOR Luteotropic stimulus which transforms and estrous cycle into pseudopregnancy by prolonging progesterone secretion from the corpus luteum. Moreover, if LH is important for progesterone secretion, no changes were observed in the pattern of LH secretion which can account for the rescue of the corpus luteum.

The control of progesterone secretion during the estrous cycle and early pseudopregnancy in the rat: prolactin, gonadotropin and steroid levels associated with rescue of the corpus luteum of pseudopregnancy.

Cervical stimulation in the rat institutes a pattern of prolactin secretion consisting of two daily surges, one diurnal and one nocturnal, which continue for the greater part of pseudopregnancy. This contrasts with the diestrous day 1–2 interval of the estrous cycle wherein prolactin levels are low and relatively unchanging. A variety of noxious procedures such as aortic cannulation and serial blood sampling, sham ovariectomy and sham surgical cuts in the hypothalamus selectively and temporarily suppresses the diurnal prolactin surges of pseudopregnancy; the nocturnal surges remained unaffected. In the absence of the ovaries (removed on day 0 of pseudopregnancy) the diurnal prolactin surges have disappeared no later than day 5, whereas the nocturnal surges are present at day 6 but have disappeared by day 10. Hypothalamic retrochiasmatic cuts abolish immediately both surges. These results demonstrate the existence of an apparently unique kind of neuroendocrine reflex, copulation-induced, which results in r...

Ovarian and hypothalamic control of the daily surges of prolactin secretion during pseudopregnancy in the rat.

The patterns of prolactin secretion during the estrous cycle and pseudopregnancy were determined in rats bearing chronic aortic catheters from which blood samples were withdrawn at 2-hr intervals throughout both reproductive states. Prolactin concentrations were determined by radioimmunoassay. Except for the spontaneous proestrus surges observed at the beginning and end of the blood collection, plasma prolactin concentrations during the estrous cycle were low, never rising above 10 ng/ml. In pseudopregnant animals, prolactin concentrations were highly erratic but significantly elevated during the 24 hr period following cervical stimulation. Beginning on day 1 and at approximately 24-hr intervals thereafter through day 11, a surge of prolactin secretion occurred, beginning at 0100 hr, peaking at 0300–0500 hr and terminating by 0900–1100 hr. Maximal mean prolactin values during the surges ranged from 40–110 ng/ml. These daily nocturnal surges of pseudopregnancy alternate daily with a period from 1100 hr to ...

The pattern of prolactin secretion during pseudopregnancy in the rat: a daily nocturnal surge.

During the estrous cycle of the rat, plasma prolactin concentrations are increased significantly only on the afternoon and evening of proestrus. This proestrus surge of prolactin secretion can be inhibited by the administration of estradiol antiserum on the day before proestrus (diestrus-2). In the present study the role of gonadotropin secretion at diestrus-2 (D-2) in regulating this estrogen secretion and consequently the proestrus surge of prolactin secretion was studied using a rabbit anti-ovine LH serum (LH-AB). In vitro, the antiserum reacted strongly with radioiodinated rat LH, less with rat FSH and not at all with rat prolactin. All rats were bled on proestrus from an aortic catheter at 1–2 hr intervals and plasma levels of prolactin were determined by radioimmunoassay. In controls treated with normal rabbit serum, proestrus prolactin levels began to rise by 1300 hr, plateaued between 1500–2100 hr and returned to baseline by 0100 hr on estrus. Intraperitoneal injection of 0.1 ml of LH-AB at 1000 h...

M. E. Freeman

Papers

The control of progesterone secretion during the estrous cycle and early pseudopregnancy in the rat: prolactin, gonadotropin and steroid levels associated with rescue of the corpus luteum of pseudopregnancy.

Ovarian and hypothalamic control of the daily surges of prolactin secretion during pseudopregnancy in the rat.

The pattern of prolactin secretion during pseudopregnancy in the rat: a daily nocturnal surge.

Regulation of the Proestrus Surge of Prolactin Secretion by Gonadotropin and Estrogens in the Rat